Category Archives: Genetic medicine

Tessara Therapeutics Cambridge, Mass.-based Tessara Therapeutics tapped Howard Liang as president and chief executive officer. Additionally, the company also expanded its leadership team with multiple appointments. Madhusudan Peshwa was named Chief Technology Officer for Cell Therapy;Bill Querbes was tapped as Senior Vice President of Therapeutic Discovery & Translational Sciences; Cecilia Cotta-Ramusino was promoted to Senior Vice President of Platform Development; Vikram Ranade was named Senior Vice President of Corporate Development; David Pollard was named Head of Bioprocess, and Steve Garbacz was tapped as Head of Finance. Prior to joining Tessara, Liang was Chief Financial Officer and Chief Strategy Officer at BeiGene for six years.

Before BeiGene, Liang spent 10 years at Leerink Partners, where he was Managing Director and Head of Biotechnology Equity Research. Peshwa joined Tessara in May 2021 after serving as CTO at Mana Therapeutics Peshwa is responsible for developing the strategy and executing the operating plan encompassing the design, development, and manufacture of Tessaras proprietary mobile gene element engineered cell therapy product portfolio. Bill Querbes joined Tessara in April of 2021 as Senior Vice President of Therapeutic Discovery and Translational Sciences. Before that, he held the position of Vice President and Fabry Program Lead at AVROBIO. Cecilia Cotta-Ramusino joined Tessara in 2019 as the Head of Platform Development. Cotta-Ramusino was the first employee at insitro where she was the Head of Functional Genomics. Prior to insitro, she was one of the first scientists hired at Editas.Ranade joined Tessara in 2020 as the Head of Corporate Development.

In this role, he drives corporate strategy, business development, and investor relations for Tessara. He was previously at McKinsey & Company, where he was an Associate Partner in the healthcare practice. Pollard, the head of Bioprocess, has over 25 years of bioprocess development. He has held roles at Merck & Co. and Sartorius. Pollard will help Tessara drive digital workflows and high throughput automation to accelerate sustainable gene therapy process development. Steve Garbacz joined Tessara in 2021 as the Head of Finance. He has more than 25 years of experience in financial management for a range of companies, including Biogen, Epizyme, Spero, and Anika.

AbCellera Neil Berkley has been named Chief Business Officer of AbCellera. Berkleys role will include leading the strategy and continued growth of AbCelleras partnership business, which currently includes a diverse portfolio of more than 100 programs with drug developers of all sizes. He joins AbCellera from Halozyme Therapeutics, where he served as Vice President, Head of Business Development. Berkley held leadership roles at Axerovision, COI Pharmaceuticals, Acadia Pharmaceuticals, Cadence Pharmaceuticals, and GSK. He also cofounded Mpex Pharmaceuticals, which was acquired by Aptalis, and Vaxiion, a clinical stage bladder cancer company.

Pierre Fabre Francesco Hofmann was appointed Head of R&D at Pierre Fabre Medical Care. Hofmannwilloversee theGroup's innovation strategy for pharmaceuticals (oncology, dermatology, rare diseases, health care). Before joining the Pierre Fabre Group, Hofmann had been workingas Global Head of Oncology Drug Discoveryfor Novartis. In this leadership role, hecoordinatedthe discovery andprogression intoclinical development of no less than twelve new cancer drugs. Hofmann'sprimarymission will be toaccelerate the delivery of new therapeuticstodevelop the Group's R&D portfolio in pharmaceuticals, through a combination of in-house projects and external partnership opportunities.

Sherlock Biosciences Bryan Dechairo was named president and CEO of Cambridge, Mass.-based Sherlock. He succeeds co-founder Rahul Dhanda, who willcontinue to serve as a board member until the end of 2021 and then as strategic adviser in 2022.Dechairo joins Sherlock from Myriad Genetics, where he was executive vice president of clinical development. Before joining Myriad, he was CMO, chief scientific officer and senior vice president of research and development at Assurex Health, which was acquired by Myriad in 2016. Prior to Assurex Health, Dechairo held roles of increasing responsibility at Medco Health Solutions, Pfizer and other diagnostic and therapeutics companies.

Atsena Therapeutics Jennifer Wellman was appointed to the board of directors of N.C.-based Atsena Therapeutics. Wellman is the Chief Operating Officer of Akouos, Inc., a precision genetic medicine company. Prior to Akouos, Wellman was Head of Product Development Strategy at Spark Therapeutics, Inc., now a subsidiary of Roche Holding AG, where she was also a co-founder. Previously, Wellman was the Director of Regulatory Affairs for the Center for Cellular and Molecular Therapeutics at Childrens Hospital of Philadelphia.

Eleusis London-based Eleusis tapped four members for its board of directors. David Socks, former CEO of Phathom Pharmaceuticals, joined as chairman of the board. Robert Hershberg, former CBO and CSO of Celgene; John Tucker, CEO of SC Pharmaceuticals; and Esther van den Boom, Managing Partner at van den Boom & Associates also joined.

H1 New York-based H1 announced Mohak Shah has joined the company as SVP of Data Science and Learning. Before joining H1, he was the Vice President of AI and ML at LG Electronics, and prior to that was the Head of Data Science at Bosch.

Renovacor Jiwen Zhang was named senior vice president of regulatory affairs and quality assurance at Philadelphia-based Renovacor, Inc. She most recently served as vice president, head of regulatory affairs at Passage Bio, Inc., an AAV-based gene therapy company. Prior to her time at Passage Bio, Zhang worked as executive director, head of regulatory affairs at Tmunity Therapeutics, Inc. Zhang also previously worked at GE Healthcare and was responsible for building a regulatory affairs function to support the companys newly formed cell technology and regenerative medicine business. Before joining GE Healthcare, Zhang held roles of increasing responsibility at several companies including Merck and Co. Inc., Wyeth Pharmaceuticals (now Pfizer) and Sanofi.

Opiant Pharmaceuticals Matthew Ruth was named Chief Commercial Officer of Opiant Pharmaceuticals. From 2015 until 2019,Ruthwas responsible for building out theU.S.Operational, Commercial, Government Affairs and Medical Affairs team in preparation for the launch and commercialization of Opiants branded nasal naloxone spray. Prior to his work in the opioid overdose space,Ruthwas Chief Operating Officer for RightCare Solutions, a medical technology company. Earlier in his career,Ruthwas Vice President of Azur Pharma. From 2006 to 2007, he was Vice President forAvanir Pharmaceuticals. Prior to that, he held positions of increasing responsibility at Allergan.

Glytec Jordan Messler was named CMO of Waltham, Mass.-based Glytec. In this new role, Messler will be responsible for spearheading continuous improvement initiatives for Glytecs clinical strategy and product development while supporting the delivery, customer, quality and regulatory teams to ensure ethical and safe glycemic management best practices. Messler joined Glytec in October 2018 as the Executive Director of Clinical Practice. Before Glytec, he was the Medical Director for the Morton Plant Hospitalist group.

T-knife Therapeutics Megan Baierlein was named COO of Bay Area-based T-knife. Baierlein was most recently the senior vice president and COO at Audentes Therapeutics, overseeing program management, clinical operations, and general and administrative functions. Prior to Audentes, Baierlein served as executive director of program management at Ultragenyx Pharmaceutical, Inc. Before that, she held management positions at BioMarin in both program management and clinical operations. Earlier in her career, Baierlein held roles of increasing responsibility at Genentech and Elan Pharmaceuticals.

Ji Xing Pharmaceuticals Shanghai-based Ji Xing tapped Joseph Romanelli as CEO. Romanelli has more than 25 years of biopharmaceutical and biotechnology experience, nearly all with Merck & Co., Inc. Most recently, he served as the President of MSD China for more than four years, where he oversaw over 20 product launches, including Keytruda and Gardasil. From an industry and organizational perspective, he was named a Top Ten Pharma Leader of the Year in 2019 by the National Healthy China Forum and managed the companys more than 5,000 employees in the market. He also briefly served as President of U.S. Human Health at Merck overseeing the companys largest market by revenue. Previously, Romanelli held senior roles, including Vice President of Investor Relations.

Hillstream BioPharma Scott J. Dixon, Associate Professor of Biology at Stanford University and Faculty Fellow of Stanfords ChEM-H initiative and Member at Stanford Cancer Institute, joined the Scientific Advisory Board of Hillstream BioPharma.

Certara Nicolette D. Sherman was named Chief Human Resources Officer at Certara. Most recently, Sherman was CHRO at Oyster Point Pharma. Prior to that, she served in multiple roles at Sanofi for 12 years, including Vice President of North American Human Resources Operations and Vice President of Global Leadership Development.

BeyondSpring Brendan Delaney, the Chief Commercial Officer of Constellation Pharma, was appointed to the BeyondSpring Board of Directors. Prior to joining Constellation, Delaney was the CCO at Immunomedics, where he led the buildout of the marketing, sales, market access and commercial operations teams. Previously, he served as Vice President of U.S. Hematology-Oncology at Celgene Corporation. Prior to joining Celgene, he held various commercial roles at both Novartis Oncology and Genentech, where he led several successful product launches for blockbuster brands.

Cygnal Therapeutics Timothy Zheng joined Cygnal Therapeutics as Senior Vice President ofBiology. Zheng joins Cygnal from Boehringer Ingelheim, where he was a Highly Distinguished Research Fellow. He also served as a Member of the U.S. Research Site Leadership Committee and as Executive Director, Immune Modulation. Prior to Boehringer Ingelheim, he held a number of roles at Biogen and Biogen Idec over a 17-year period with increasing responsibilities, most recently as Director of Immunology and then Director of Neuroimmunology.

Byondis Timo van den Berg was named Senior Director of Immuno-Oncology R&D at Netherlands-based Byondis BV. Most recently he serves as head and principal investigator, Immunotherapy Laboratory, Department of Molecular Hematology at Sanquin Research, a non-profit organization responsible for the blood supply in the Netherlands. Since 2017, Van den Berg has been professor of Immunotherapy at Vrije Universiteit. Van den Berg is a member of many boards, including Amsterdam Infection and Immunity Institute and Cancer Center Amsterdam.

FINN Partners Kristie Kuhl was promoted to managing partner, Global Health Practice Leader for FINN Partners, an industry media organization. Kuhl joined Finn Partners in 2015 as U.S. Pharma and NY Health Head. She came to FINN after serving as an executive vice president at agencies Cohn & Wolfe and Makovsky, where she drew on her knowledge of pharma marketing, regulatory law, patient advocacy and the U.S. reimbursement system to advance breakthrough therapies.

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Movers & Shakers, July 16 | BioSpace - BioSpace

Esoteric testing is the analysis of 'rare' molecules or substances. It is not performed in a routine clinical laboratory. These test are performed when there is requirement of additional information external routine lab testing, for proper diagnosis of disease, establish a prognosis or select and supervise a therapeutic treatment. Esoteric testing requires skilled personnel to perform the test and analyze the results due to usage of sophisticated chemicals and instruments. The tests are performed by specialized and independent clinical reference laboratories owing to high cost. It is not feasible for physician office laboratories and hospitals to perform these tests in-house. The test are regulated by regulatory stringent regulatory framework. These tests are not performed regularly.

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Based on test type, the global esoteric testing market has been segmented into genetics, endocrinology, immunology, molecular diagnostics, microbiology, oncology, serology, and toxicology. Molecular diagnostics is the fastest growing segment of the market, followed by the immunology and oncology segments, owing to increased prevalence of rare and genetic diseases and high demand for personalized medicine treatment. In terms of technology, the esoteric testing market has been segmented into chemiluminescence, ELISA, mass spectrometry, real time PCR, and flow cytometry. The chemiluminescence segment is expected to witness strong growth, followed by ELISA, because it is the most widely used technology in esoteric testing due to high efficiency and small sample required for testing. The real time PCR segment is expected to be driven by rise in prevalence of genetic disease and increase in demand for genetic testing. Growing use of information technology has allowed instant and efficient data transfer. These developments will provide more efficient results and improved patient care creates huge demand for esoteric testing market. Complex diseases difficult to diagnose and treat through conventional methods are diagnosed using esoteric testing. Rising prevalence of such complex and rare medical diseases is expected to contribute to the growth of the esoteric testing market. Additionally, high investments in proteomics, increasing demand for personalized medicine, and genomics boost the growth of the esoteric testing market. However, stringent government regulations and dearth of qualified and trained professionals are likely to restrain the esoteric testing market.

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In terms of region, the global esoteric testing market can be classified into North America, Latin America, Europe, Asia Pacific, and Middle East & Africa. North America dominates the esoteric testing market, followed by Europe, due to higher incidence and prevalence rate, growing awareness about early disease detection, and quick adoption of sophisticated instruments. Asia Pacific is an emerging market for esoteric testing due to increasing prevalence of disease, gradual development of medical infrastructure, rising awareness, and significant patient pool with unmet medical needs. However, high cost, lack of availability of trained personnel, and poor patient awareness are factors restraining the esoteric testing market in regions such as Middle East & Africa and Latin America.

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Major players operating in the esoteric testing market include Laboratory Corporation of America Holdings, OPKO Health, Inc., ARUP Laboratories, Genomic Health, Inc., Quest Diagnostics, American Medical Laboratories, Gold Standard Diagnostics Corp, and ZeptoMetrix Corporation.

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Esoteric Testing Market: Chemiluminescence segment is expected to witness strong growth - BioSpace

MENLO PARK, Calif., July 20, 2021 (GLOBE NEWSWIRE) -- Pacific Biosciences of California, Inc. (Nasdaq: PACB)(Pacific Biosciences or PacBio), a leading provider of high-quality, long-read sequencing platforms, and Invitae Corporation (NYSE: NVTA), a leading medical genetics company, today announced an intent to expand their multi-year collaboration to develop a production-scale high-throughput HiFi sequencing platform to include the sequencing technology developed by Omniome, Inc.

The expansion of the collaboration is expected to add the short read sequencing technology enabled by Sequencing by Binding (SBB) chemistry upon close of PacBios proposed acquisition of Omniome, and contingent upon PacBios and Invitaes agreement of associated terms. Omniomes novel and highly differentiated sequencing technology promises significant improvement in raw base accuracy over traditional next generation sequencing products enabling the potential for more precise and sensitive molecular diagnostics. PacBio and Invitae intend to work together to leverage the improved accuracy and sensitivity of SBB chemistry to further advance cancer diagnostics and pathogen detection. Additionally, the parties intend to work together to explore novel methods of integrating SBB chemistry with PacBios HiFi genomes.

We believe access to both of these technologies will accelerate the adoption of long read sequencing techniques in clinical whole genome applications, providing deeper insight into the genome and lower the overall cost of analysis, said Christian Henry, CEO and President at PacBio. Scientists and clinicians rely on accurate short reads and accurate long reads to conduct their science and answer their specific questions. We seek to deliver the most advanced sequencing solutions and are excited that we might expand our development collaboration with Invitae to broadly enable their clinical NGS sequencing.

In partnering with the PacBio team, we are pleased with our progress toward a new generation of innovative whole genome-based offerings, and look forward to expanding that effort to include the highly differentiated SBB chemistry, said Sean George, Co-Founder, President and Chief Executive Officer of Invitae. By combining SBB with PacBios HiFi Sequencing, the opportunity and utility of next generation sequencing technologies can be expanded for patients in the clinical setting with improvement in accuracy and reduction in costs.

The expansion of the collaboration is expected to begin in the second half of 2021 once PacBios acquisition of Omniome, Inc. is complete.

About Pacific BiosciencesPacific Biosciences of California, Inc. (NASDAQ: PACB) is empowering life scientists with highly accurate long-read sequencing. The companys innovative instruments are based on Single Molecule, Real-Time (SMRT) Sequencing technology, which delivers a comprehensive view of genomes, transcriptomes, and epigenomes, enabling access to the full spectrum of genetic variation in any organism. Cited in thousands of peer-reviewed publications, PacBio sequencing systems are in use by scientists around the world to drive discovery in human biomedical research, plant and animal sciences, and microbiology. For more information, please visit http://www.pacb.com and follow @PacBio.

About InvitaeInvitae Corporation (NYSE: NVTA) is a leading medical genetics company whose mission is to bring comprehensive genetic information into mainstream medicine to improve healthcare for billions of people. Invitaes goal is to aggregate the worlds genetic tests into a single service with higher quality, faster turnaround time, and lower prices. For more information, visit the companys website at invitae.com.

PacBio products are provided for Research Use Only. Not for use in diagnostic procedures.

Forward-Looking Statements This press release may contain forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and the U.S. Private Securities Litigation Reform Act of 1995, including statements relating to the intended expansion of the collaboration between PacBio and Invitae to include Omniomes short read sequencing technology, including the expected timing of such expansion; the potential for PacBio to enable Invitaes clinical NGS sequencing capabilities; PacBio and Invitae agreeing to associated terms of such collaboration expansion; the potential cost reductions, and potential increases in accuracy and sensitivity, associated with the use of SBB technology; the potential use of SBB technology for more precise and sensitive molecular diagnostics, including cancer diagnostics and pathogen detection; potential novel methods of integrating SBB chemistry with PacBios HiFi genomes; expectations that access to both SBB and HiFi sequencing technologies may accelerate adoption of long read sequencing techniques in clinical whole genome applications; expectations regarding the timing of the closing of PacBios proposed acquisition of Omniome, and increase the rate of identification of, potential disease-causing genetic variants in rare disease the potential of HiFi data, the applications, insights, and attributes of SMRT sequencing technology, and the benefits of PacBio sequencing. Readers are cautioned not to place undue reliance on these forward-looking statements and any such forward-looking statements are qualified in their entirety by reference to the following cautionary statements. All forward-looking statements speak only as of the date of this press release and are based on current expectations and involve a number of assumptions, risks and uncertainties that could cause the actual results to differ materially from such forward-looking statements. Readers are strongly encouraged to read the full cautionary statements contained in the Companys filings with the Securities and Exchange Commission, including the risks set forth in the companys Forms 8-K, 10-K, and 10-Q. The Company disclaims any obligation to update or revise any forward-looking statements.

Contacts

Investors:Todd Friedman+1 (650) 521-8450ir@pacificbiosciences.com

Media:Jen Carroll+1 (858) 449-8082pr@pacificbiosciences.com

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Pacific Biosciences and Invitae Announce Intent to Expand Collaboration - BioSpace

A new first of its kind institution aimed at enhancing local genomic research as well as diagnosing and treating patients with genetic disorders has been unveiled in the United Arab Emirates (UAE).

The Center for Genomic Discovery is a joint venture between the Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU) and the Al Jalila Genomics Center of the Al Jalila Childrens Specialty Hospital (AJCH).

The necessary interdisciplinary activities including patient recruitment, genomic data analysis, and functional characterisation cannot be undertaken without the Center, its founding institutions, and the interdisciplinary ecosystem they have created, said Fahad Ali, Assistant Professor of Molecular Biology at MBRU. At the Center, functional experiments will be designed to characterise any novel candidate genes or mutations, to establish new gene-disease associations, and to explore potential therapeutic targets.

And work has already started with one family, offering promising progress, said Stefan Du Plessis, founding Dean of Research and Graduate Studies at MBRU and a member of the Centers Steering Committee.

At least one novel gene has been identified by whole-exome sequencing a complex genomic test which surveys all 20,000+ human genes in search for tiny changes which might be disease causing, he said. Functional analysis is still ongoing but preliminary data strongly suggests a role in disease. We have also identified patients outside the UAE, in the Gulf region, with the same clinical conditions, mutations and gene.

We are now establishing collaborations with researchers from those sites to characterise this gene. The fact that patients from different backgrounds with similar clinical features have mutations in the same gene further establishes a potential new gene-disease discovery.

WHY IT MATTERS

Speaking at Arab Health 2021, Amer Sharif, Vice Chancellor of MBRU, described the formation of the centre as a major milestone for healthcare research in the UAE.

These are life-changing outcomes that underline the power of research and the role of MBRU and our academic health system partners as research-intensive institutes, he said. The establishment of the Center of Genomic Discovery through an integrated academic health system will allow us to innovate in genomics application and gene discovery. This will also enable us to realise our vision of advancing health through cutting-edge academic research and nurturing future scientists serving individuals and communities in the UAE and the region.

The Center for Genomic Discovery will reportedly seek to engage undiagnosed pediatric patients with suspected hereditary disorders whose clinical genomic testing at Al Jalila Childrens such as whole-exome sequencing and chromosomal microarrays failed to identify any definitive genetic causes.

THE LARGER CONTEXT

The launch of the centre coincides with the formation of the board of the Emirati Genome Program, whose mission is to provide preventive and personalised healthcare for the Emirati population.

Headed by His Highness Sheikh Khalid bin Mohamed bin Zayed Al Nahyan, Member of the Abu Dhabi Executive Council and Chairman of the Abu Dhabi Executive Office, the Emirati Genome Program is reportedly being designed to enable precise and customised medical treatment that will support a more robust healthcare system in the UAE.

MBRUs Sharif is a member of the board.

Meanwhile, AJCSH has also announced it is to formulate a steering group to study the workflow of genome sequencing in an intensive care setting. The hospital has partnered with Illumina Netherlands BV to develop this practical knowledge improving the use of testing, and fostering greater understanding of best-use cases, clinical indicators and the health economics of genome sequencing in this specialised setting.

There is increasing evidence for rapid, efficient and cost-efficient genome sequencing in newborns and babies that will save lives, said Mohamed Al Awadhi, COO of AJCH. The application of next-generation sequencing has revolutionised the process of making complex diagnoses in paediatric medicine, significantly shortening the time for accurate diagnosis and optimal clinical management in critically ill children.

Thanks to the support of our partners and stakeholders, this working group will once again push the boundaries in the quest to save young lives.

ON THE RECORD

This is a major development for Dubai and the UAE, said Ahmad Abou Tayoun, Director of Al Jalila Childrens Genomics Center and Associate Professor of Genetics at MBRU. The new Center leverages the clinical, genomics, and functional research infrastructure and human resources at Al Jalila Childrens and MBRU to propel interdisciplinary activities.

Our clinicians and researchers are experts in their respective fields who can help resolve undiagnosed patients with highly suspected inherited disorders. Furthermore, the Center will create a training and research site for Masters and Ph.D. students, as well as post-doctoral fellows at MBRU.

He added: Ultimately, the Centers main goal is to make novel genetic discoveries in the pediatric patient population in the UAE and the region, and leverage these discoveries to develop new diagnostic tools and uncover personalised pathways to restore normal phenotypes in affected patients.

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Center for Genomic Discovery launched in the United Arab Emirates - Mobihealth News

Background

Lung cancer is the most common solid tumor and has the highest morbidity and mortality worldwide. According to the latest cancer-epidemiology data, 0.815 million new cases and 0.715 million new deaths due to lung cancer are observed in China currently.1 As the most common histological subtype, nonsmall cell lung cancer (NSCLC) accounts for approximately 85% in lung cancer.2 Recently, targeted drugs with different mechanisms of action were developed based on common somatic gene-mutation profiles with significant survival benefits.3 Unfortunately, approximately half the patients with NSCLC in China lack one potentially significant driver-gene mutation, and correspondingly only platinum-based chemotherapy regimens are available as first-line treatment.4 Chemotherapy efficacy is dismal, with objective response rate (ORR) 20%30% and median progression-free survival (PFS) 45 months.5 Single-agent chemotherapy with docetaxel, pemetrexed, gemcitabine, and immunotherapy are alternative second-line treatment options, with additional benefits in prolonging survival after first-line treatment.6

However, the advantages of traditional second-line treatment are limited currently. Immunotherapy drugs have been licensed in recent years, and the low ORR of PD1/PDL1 inhibitors has exhibited that patients who could benefit from an immunotherapy drug are thus also limited.7 Consequently, patients with advanced NSCLC are in urgent need of therapeutic drugs upon disease progression after standard treatment. Angiogenesis was identified as an important therapeutic strategy for solid tumors and was proven to be an essential condition in the process of tumor growth according to the theory of Folkman in 1971.8 Antiangiogenic drugs exhibit potential anticancer activity in treatment show advanced NSCLC. Bevacizumab and ramucirumab exhibit potential survival benefits for patients with NSCLC as first-line and second-line treatment, respectively.9 In terms of antiangiogenesis multitargeted tyrosine-kinase inhibitors (TKIs), anlotinib has been a standard regimen for third-line treatment in China since 2018.10 As a similar antiangiogenesis TKI, apatinib has been approved as subsequent-line treatment for advanced or metastatic gastric cancer.11 Considerable research has been done on apatinib in the treatment of NSCLC, colorectal cancer, and breast cancer.12 Interestingly, as far as we know, the ORR of antiangiogenic targeted drugs was disappointing. The ORR of sorafenib, anlotinib, and fruquintinib monotherapy as third-line treatment of advanced NSCLC is only 4.9%, 9.18%, and 16.4%, respectively.13 Consequently, great individual differences regarding the efficacy of antiangiogenic targeted drugs have been observed clinically. Therefore, exploration of biomarkers that could predict the efficacy of apatinib is necessary.

PDL1 is one of the most important biomarkers for the prognostic prediction of immunotherapy.14 A study has shown that higher PDL1 expression predicts superior clinical outcome with PD1/PDL1 inhibitors.15 Although patients with positive PDL1 expression can benefit from PD1/PDL1 inhibitors, the association between the prognosis of patientsadministered antiangiogenic targeted drugs and PDL1 expression status remains unknown.16 Wu et al investigated the association between PDL1 polymorphisms and prognoses of patients with gastric cancer. The CC genotype of rs822336 resulted in superior prognoeis for all GC patients and those without postoperative chemotherapy.17 Interestingly, a recent study Su et al investigated the association between PDL1 genetic variation and the prognosis of patients with R0-resection colorectal cancer who received capecitabine-based adjuvant chemotherapy in the real world. The conclusion indicated that the PDL1 901T>C polymorphism might be a valuable biomarker for patients with CRC receiving capecitabine-based adjuvant chemotherapy.18 Furthermore, a prior study indicated that VEGFR inhibitors could possess immunomodulatory properties that might result in antitumor activity and reduce the function of regulatory T cells and CD14-positive immunosuppressive monocytes, thus increasing cytokine production from effector T cells in response to antigen stimulation and activating the innate immunoresponse.19 Consequently, VEGFR inhibitors could potentially play an synergetic role with immunotherapy.

However, the association between PDL1 genetic variation and efficacy in patients with advanced NSCLC who have received apatinib treatment is unknown. Consequently, our study aimed to investigate the association between PDL1 genetic variation and the efficacy of apatinib monotherapy in patients with previously treated advanced NSCLC. Additionally, the potential correlation between PDL1 genetic variations and PDL1 gene-mRNA expression in biopsied cancer-tissue specimens was explored.

Given that apatinib has been approved in Chinese mainland for 5 years, with considerable numbers of patients receiving apatinib treatment, our study was designed as a retrospective analysis. Consequently, patients with advanced NSCLC who had failed after previous systemic treatment from January 2015 to December 2019 in the Department of Respiratory Medicine of the Fourth Hospital of Hebei Medical University participated. Eligibility criteria were diagnosis of NSCLC with pathological staging of IIIB or IV, age 18 years Eastern Cooperative Oncology Group (ECOG) performance status 02, apatinib monotherapy used for those who had failed after or were unable to tolerate previous systemic standard treatment, at least one measurable target lesion based on response evaluation criteria in solid tumors (RECIST 1.1) available, and appropriate renal, hepatic, and hematopoietic function to receive apatinib treatment. Exclusion criteria were new diagnosis or uncontrollable central nervous system metastases, concomitant with other tumors or serious diseases, hemoptysis >50 mL/day, and efficacy data evaluation not available. The flow chart of this study is given in Figure 1. Finally, a total of 148 patients with advanced NSCLC was enrolled in this study. The primary focus of this study was associations between PDL1 polymorphisms, objective response rate (ORR), progression free survival (PFS), overall survival (OS), and adverse reactions. The study was conducted in accordance with the Declaration of Helsinki and approved by the ethics committee of the Fourth Hospital of Hebei Medical University. Informed consent was obtained from each enrolled patient.

Figure 1 Flowchart of the study.

Initial dosage of apatinib was 500 mg or 750 mg per day orally continuously for 28 days until disease progression or intolerable adverse reactions. Dosage was determined based on baseline physical conditions: body-surface area (BSA), ECOG score, and age, which was up to the clinical experience of the investigators. Dosage was adjusted based on the hematologic or nonhematologic toxicity during treatment. Treatment was suspended when life-threatening toxic reactions occurred. Efficacy was assessed based on RECIST 1.1 criteria.20 Changes in target lesions were assessed after completion of the first cycle with computed-tomography scans and then every two cycles or when necessary. Safety profiles during treatment were documented using Common Terminology Criteria for Adverse Events version 4.03 to record hematologic and nonhematologic events that might be drug-related.21 Adverse reactions with incidence of 10% were recorded and analyzed.

Approximately 4 mL peripheral blood prior to apatinib treatment from each patient was collected and genomic DNA extracted using phenol chloroform. In terms of the PDL1-polymorphism analysis, those included were rs2297136, rs822336, and rs822337. However, only rs2297136 was significantly associated with clinical outcomes on preliminary analysis. Consequently, following analysis was performed based on rs2297136-genotype status. The rs2297136 polymorphism was genotyped using PCR-RFLP. The PCR product of rs2297136 was amplified firstly, with forward primer 5-GCTCCCTGTTTGACTCCATC-3 and reverse primer 5- TTTTTCCCCAGACCACTTCC-3. The product was 274bp, and a 2 L PCR products were digested using the restriction enzyme ApaI (Thermo Fisher Scientific, Waltham, MA, USA). Polymorphism genotypes were determined by the size of PCR bands: TT genotype, one 274 bp band; TC genotype, one 274 bp band, one 158 bp band, and one 116 bp band; and CC genotype, one 158 bp band and one 116bp band. Some genotyping results for rs2297136 were confirmed using ionizationtime-of-flight mass spectrometry (Sequenom, SanDiego, CA, USA).

Cancer tissue-specimens were collected from 85 randomly selected samples from the 148 patients. A total of 68 specimens were available for subsequent analysis and preserved in liquid nitrogen. All RNA samples were extracted using Trizol reagents and stored at 80C for mRNA-expression analysis. A total of 500 ng RNA extracted from the specimens was used as the template for reverse-transcription PCR to prepare the first stand of cDNA using a PrimeScript RT reagent kit. Relative quantitative analysis of PDL1-mRNA expression was carried out using a LightCycler 480 withn SYBR premix Ex Taq system. The forward primer was 5-TTCAATGTGACCAGCACACTGAG-3, the reverse primer 5-TTTTCACATCCATCATTCTCCCT-3. PDL1-mRNA expression was detected using comparative 2Ct. GAPDH-mRNA expression was used as an endogenous control.

Variables in this study were analyzed using SPSS 25.0. Significance of proportional and continuous variables based on rs2297136-genotype status was assessed using the #x1D712;2 and MannWhitney U nonparametric tests, respectively. Primary analysis was performed on correlations between PFS and rs2297136-genotype status. KaplanMeier curves were used to draw the PFS and OS curves based on rs2297136-genotype status. Survival differences were compared using log-rank tests. PFS was defined as time from apatinib administration to progression or death from any cause, whichever occurred first. OS was defined as time from apatinib administration to death from any cause. For those without progression or death by the end of the study follow-up, survival end points were censored as per the date of last follow-up.22 Cox regression was performed for PFS in the multivariate analysis. P<0.05 was considered statistically significant.

Baseline characteristics of the 148 patients are shown in Table 1. Median age was 58 (2879) years, 96 patients were men (64.86%). Pathological stage IV was observed in 140 patients (94.59%). ECOG 0 score was noted in 39 patients (26.35%). Nonsmokers/former smokers numbered 107 (72.30%). The most common histology of the patients was adenocarcinoma, with 114 cases (77.03%), and squamous-cell carcinoma, with 28 cases (18.92%). Numbers of patients with fewer than or equal to three and greater than three sites were 92 and 56, respectively. Positive driver-gene mutation status was confirmed in 56 patients (37.84%): 50 patients had EGFR mutations, four ALK rearrangements, and two ROS1 rearrangements. History of treatment with second and further lines was observed in 43 cases and 105 cases, respectively. A total of 92 patients (62.16%) had received targeted drug therapy. Interestingly, ten patients (6.76%) had received antivascular TKI treatment. It should be noted that eleven patients had been treated with PD1/PDL1 inhibitors. Initial dosage of 500mg and 750mg of apatinib was observed in 97 and 51 patients, respectively.

Table 1 Baseline characteristics based on PDL1 rs2297136 genotype status

rs2297136 was of clinical significance on subsequent analysis. The germ-line mutation frequency of rs2297136 were TT genotype 103 cases (69.59%), TC genotype 40 (27.03%), and CC genotype five (3.38%), with minor-allele frequency 0.17. Distribution of the three genotypes was in accordance with the HardyWeinberg Equilibrium (P=0.649). In view of the relatively rare frequency of the CC genotype, CC and TC were merged for subsequent analysis. As shown in Table 1, patients with TT and TC/CC genotypes were well balanced with similar baseline characteristics.

The best overall response of each patient was recorded for efficacy analysis. No complete response or partial response was observed in 26 cases, stable disease noted in 76, and progressive disease in 46 based on RECIST version 1.1. ORR was 17.6% (95% CI 11.8%-24.7%) and disease-control rate (DCR) 68.9% (95% CI 60.8%-76.3%). A waterfall plot for the best percentage change in target lesions is shown in Figure 2.

Figure 2 Waterfall plot of best change (reductions in sum of target-lesion diameters) from baseline.

The last follow-up in this study was in September 2020. Median follow-up duration was 10.3 (136) months. A total of 142 patients had had PFS or had died at data cutoff. Therefore, PFS at data maturity was 95.9%. As exhibited in Figure 3, median PFS patients with NSCLC receiving apatinib was 3.8 (95% CI 3.134.47) months. In terms of OS, 137 patients had died at data cutoff. Consequently, OS at data maturity was 92.6%. As exhibited in Figure 3, median OS was 10.5 months(95% CI 9.0611.95).

Figure 3 Progression-free survival and overall survival.

We further analyzed PFS based on baseline-characteristic subgroups, and univariate analysis of this is shown in Table 2. Obviously, ECOG score and number of metastasis sites were significantly associated with PFS: median PFS of patients with ECOG 0 was longer than those with ECOG 12 score (4.9 vs 3.2 months, P=0.018). Median PFS of patients with number of metastasis sites fewer than or equal to was superior to those with greater than (4.5 vs 3.2, P=0.025). As illustrated in Figure 4, median PFS of patients with TT and TC/CC genotypes of rs2297136 was 4.5 and 3.0 months, respectively (2=7.69, P=0.006). Multivariate Cox regression model was used for PFS based on baseline characteristics significant on univariate analysis (Table 2) to adjust for confounding factors. Multivariate analysis results are shown in Table 3, with significant differences confirmed for the rs2297136 polymorphism and PFS, with rs2297136 an independent factor (OR=1.47, P=0.011). Interestingly, as shown in Table 3after adjustment in Cox regression analysis, ECOG score (OR=1.52, P=0.027) and number of metastasis sites (OR=1.39, P=0.039) were independent factors in PFS.

Table 2 Univariate analysis of progression-free survival based on baseline characteristics

Table 3 Multivariate Cox regression analysis for PFS based on baseline characteristics and rs2297136 polymorphism status

Figure 4 Progression-free survival based on PDL1 rs2297136 genotype status.

In terms of association between rs2297136-genotype status and OS, as exhibited in Figure 5, median OS of patients with TT and TC/CC genotypeswas 11.6 and 9.0 months, respectively (2=3.98, P=0.04).

Figure 5 Overall survival based on PDL1 rs2297136 genotype status.

The main adverse reactions during apatinib treatment were recorded and analyzed. As presented in Table 4, common adverse reactions related to apatinib treatment were hypertension, dermal toxicity, fatigue, oral toxicity, appetite decrease, diarrhea, nausea and vomiting, and hematologic toxicity, with incidence of 45.27%, 41.89%, 37.16%, 31.76%, 31.08%, 24.32%, 17.57%, and 11.49%, respectively. As demonstrated in Table 4, no significant association was observed between adverse reactions and rs2297136-genotype status.

Table 4 Correlation analysis between PDL1 rs2297136 polymorphism and safety profile of apatinib administration

The genotype status of rs2297136 in the 68 specimens was TT genotype 47 cases (69.12%), TC genotype 19 (27.94%), CC genotype ywo (2.94%), which was similar to the genotype-frequency distribution of the 148 patients. The distribution of the three genotypes corresponded with the HardyWeinberg equilibrium (P=0.962) as well. CC and TC genotypes were merged in the subsequent analysis similarly. As exhibited in Figure 6, patients with the TC/CC genotype showed higher relative expression of PDL1 mRNA in biopsied cancer-tissue specimens than those with the TT genotype (4.0100.517 vs 2.7030.677, P<0.001). Additionally, PDL1-mRNA expression was divided into highand low PDL1expressionbased onmedian PDL1- mRNA expressionHigh and lowPDL1 were observed in 33 and 35 cases, respectively. As presented in Figure 7, patients with highPDL1 expression had a trend for worse PFS compared with those with low PDL1expression (median PFS 3.5 vs 4.6), though difference was not statistically significant (2=1.53, P=0.216).

Figure 6 Relative expression level of PDL1 mRNA based on PDL1 rs2297136 genotype status.

Figure 7 Progression-free survival of the 68 specimens from patients based on PDL1 mRNAexpression status.

Our retrospective study provided real-world evidence regarding the efficacy and safety of apatinib monotherapy for patients with previously treated advanced NSCLC. Simultaneously, genetic variation analysis suggested that clinical outcomes of patients with advanced NSCLC receiving apatinib treatment could be influenced by the rs2297136 polymorphism through mediating the PDL1-mRNA expression.

The ORR and DCR of the 148 patients with NSCLC were 17.6% and 68.9%, respectively. Median PFS was 3.8 months, slightly inferior to the first phase II clinical trial of apatinib in advanced NSCLC by Zhang et al in 2012 (ORR 20%, DCR 68.89%, and median PFS 4.7 months).23 This might be attributable to the retrospective design. The management of patients was inferior in retrospective study when compared with the clinical trials, which was demonstrated in the other retrospective study.24 These efficacy differences highlighted the gap between randomized controlled clinical trials and actual clinical practice.25 Patients with an ECOG score of 2 were included in our study as well. To our knowledge, the influence of ECOG score on prognosis has been confirmed in many studies, which indicate that higher PS scores have worse prognoses.26 Results of the multivariate Cox analysis of this study suggested that patients with ECOG scores of 12 had worse prognoses compared with those with a score of 0. However, it should be noted that median OS of our study was 10.5 months, which was slightly longer than the median OS of another apatinib study reported recently.22 The reason for this could be the continued license for PD1/PDL1 inhibitors and anlotinib in China since 2018.10 Patients with advanced NSCLC stood a good chance to choose PD1/PDL1 inhibitors and targeted drugs as subsequent treatment, which have proven to be effective and brought significant survival benefits.27

This study is the first study to focus on the correlation between the efficacy of apatinib treatment in patients with advanced NSCLCand PDL1-polymorphism analysis in Chinese patients. Interestingly, a recent study initiated by Wang et al investigated clinical outcomes and safety of apatinib in the treatment of advanced nonsquamous NSCLC and the clinical significance of KDR-gene polymorphism.22 The results suggested that clinical outcomes of treatment with apatinib might be influenced by the KDR 4397T>C polymorphism. The conclusion of that study highlighted the potential predictive value of pharmacogenomics in the clinical outcomes of patients with NSCLC receiving apatinib treatment. In terms of the polymorphism analysis in our study, minor-allele frequency of rs2297136 was 0.17, in line with the genotype frequency of the Chinese population in the NCBI database and the results of Xie et al.28 Minor-allele frequency in the Caucasian population is significantly different from that in our study, which suggests that great ethnic differences in PDL1 polymorphisms exist clinically.29 Xie et al studied 225 hepatocellular carcinoma patients, and their results suggested that the CC genotype of rs2297136 was correlated with predisposition to this cancer type. Their prognosis-analysis results were basically consistent with the results of our study. They also showed that patients with minor alleles of rs2297136 had worse prognoses. Many studies have suggested that PDL1 polymorphisms are associated with the risk of cancer.30

Recently, a retrospective analysis by Wu et al explored the association between genetic variation of PDL1 and its protein expression and prognosis in gastric cancer.17 A total of 728 gastric cancer patients were included in their polymorphism analysis, and the results suggested that rs2297136genotype A was correlated with PDL1 protein expression and superior prognosis in patients without postoperative chemotherapy, consistent with the results of our study to some extent, considering that only PDL1-mRNA expression was assessed in ours. Previous research has confirmed that PDL1- mRNA expression is positively correlated with PDL1 protein expression among patients with EGFR-mutated lung adenocarcinoma.31 Du et al explored the association between rs2297136 and predisposition toNSCLC.32 The results showed that rs2297136 influenced predisposition to NSCLC. A recent real-world studywas conducted on 315 patients with R0-resected colorectal cancer who received capecitabine-based adjuvant chemotherapy.18 The results indicated that the 901T>C TC/CC genotype conferred significantly higher mRNA expression than those with the TT genotype, which is consistent with the mRNA-expression results in our study. Additionally, it should be noted that rs2297136 was located at PDL1 3UTR, which can cause disruption in miRNA attaching to this region, perhaps leading to altered PDL1 expression at the protein level and be of prognostic significance for patients with NSCLC receiving apatinib treatment. In terms of safety profile, the common adverse reactions were hypertension, dermal toxicity, fatigue, oral toxicity, appetite decrease, diarrhea, nausea and vomiting, and hematologic toxicity, similar to the results of previous retrospective studies of apatinib regimens.22,33 The correlation analysis between the polymorphism and adverse reactions failed to show a significant difference.

Noteworthily, PDL1 is a hot-spot gene for efficacy predication of PD1/PDL1 inhibitors.34 However, the clinical significance of PDL1 expression in the prognosis of patients with advanced NSCLC receiving antiangiogenic drugs instead of immunotherapy is still unknown and thus necessary to investigate.35 The results of our study preliminarily suggested that patients with high mRNA expression of PDL1 might have worse prognosis, in line with previous studies in which patients with high PDL1 expression demonstrated worse prognosis when received EGFR TKIs36 and concurrent chemoradiotherapy treatment.37 However, the genes role in vivo is still unclear. Several clinical studies indicated that patients with high expression of PDL1 had better prognosis.38 These results might be attributed to the heterogeneity of patients included. Briefly, further in-depth prospective clinical trials are needed to explore the clinical significance of PDL1 polymorphisms.

We believe our study is of potential clinical significance for prognosis evaluation of patients with advanced NSCLC who have been treated with apatinib. Further randomized controlled clinical trials are warranted to validate the conclusions.

The present retrospective study provided real-world evidence regarding the superior efficacy and tolerable adverse reactions of apatinib monotherapy for patients with previously treated advanced NSCLC. Also, PDL1 polymorphism rs2297136 could be used as a potential biomarker for prognosis of patients with NSCLC receiving apatinib treatment.

The authors would like to express their sincere gratitude to the patients and their families for participating in this study. We thank all the staff who took part in this study.

The authors declare that there are no conflicts of interest.

1. Xu K, Zhang C, Du T, et al. Progress of exosomes in the diagnosis and treatment of lung cancer. Biomed Pharmacother. 2021;134:111111. doi:10.1016/j.biopha.2020.111111.

2. Zhang J, Mao W, Chen Z, Gu H, Lian C. Clinical Significance of Has_circ_0060937 in Bone Metastasis of NSCLC. Int J Gen Med. 2020;13:11151121. doi:10.2147/ijgm.s279023.

3. Phan TT, Ho TT, Nguyen HT, et al. The prognostic impact of neutrophil to lymphocyte ratio in advanced non-small cell lung cancer patients treated with EGFR TKI. Int J Gen Med. 2018;11:423430. doi:10.2147/ijgm.s174605.

4. Arbour KC, Riely GJ. Systemic Therapy for Locally Advanced and Metastatic Non-Small Cell Lung Cancer: a Review. JAMA. 2019;322(8):764774. doi:10.1001/jama.2019.11058.

5. Ghadyalpatil NS, Pandey A, Krishnamani I, et al. First-line management of metastatic non-small cell lung cancer: an Indian perspective. South Asian J Cancer. 2019;8(2):7379. doi:10.4103/sajc.sajc_294_18.

6. Garassino MC, Kawaguchi T, Gregorc V, et al. Chemotherapy versus erlotinib as second-line treatment in patients with advanced non-small cell lung cancer and wild-type epidermal growth factor receptor: an individual patient data (IPD) analysis. ESMO Open. 2018;3(6):e000327. doi:10.1136/esmoopen-2018-000327.

7. Huang L, Li L, Zhou Y, et al. Clinical Characteristics Correlate With Outcomes of Immunotherapy in Advanced Non-Small Cell Lung Cancer. J Cancer. 2020;11(24):71377145. doi:10.7150/jca.49213.

8. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med. 1971;285(21):11821186. doi:10.1056/nejm197111182852108.

9. Manzo A, Montanino A, Carillio G, et al. Angiogenesis Inhibitors in NSCLC. Int J Mol Sci. 2017;18(10):10. doi:10.3390/ijms18102021.

10. Han B, Li K, Wang Q, et al. Effect of Anlotinib as a Third-Line or Further Treatment on Overall Survival of Patients With Advanced Non-Small Cell Lung Cancer: the ALTER 0303 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2018;4(11):15691575. doi:10.1001/jamaoncol.2018.3039.

11. Li J, Qin S, Xu J, et al. Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Apatinib in Patients With Chemotherapy-Refractory Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction. J Clin Oncol. 2016;34(13):14481454. doi:10.1200/jco.2015.63.5995.

12. Zhao D, Hou H, Zhang X. Progress in the treatment of solid tumors with apatinib: a systematic review. Onco Targets Ther. 2018;11:41374147. doi:10.2147/ott.s172305.

13. Villaruz LC, Socinski MA. The role of anti-angiogenesis in non-small-cell lung cancer: an update. Curr Oncol Rep. 2015;17(6):26. doi:10.1007/s11912-015-0448-y.

14. Hudson K, Cross N, Jordan-Mahy N, Leyland R. The Extrinsic and Intrinsic Roles of PD-L1 and Its Receptor PD-1: implications for Immunotherapy Treatment. Front Immunol. 2020;11:568931. doi:10.3389/fimmu.2020.568931.

15. Paz-Ares L, Luft A, Vicente D, et al. Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer. N Engl J Med. 2018;379(21):20402051. doi:10.1056/NEJMoa1810865.

16. Yi M, Jiao D, Qin S, et al. Synergistic effect of immune checkpoint blockade and anti-angiogenesis in cancer treatment. Mol Cancer. 2019;18(1):60. doi:10.1186/s12943-019-0974-6.

17. Wu Y, Zhao T, Jia Z, et al. Polymorphism of the programmed death-ligand 1 gene is associated with its protein expression and prognosis in gastric cancer. J Gastroenterol Hepatol. 2019;34(7):12011207. doi:10.1111/jgh.14520.

18. Su J, Dai B, Yuan W, et al. The influence of PD-L1 genetic variation on the prognosis of R0 resection colorectal cancer patients received capecitabine-based adjuvant chemotherapy: a long-term follow-up, real-world retrospective study. Cancer Chemother Pharmacol. 2020;85(5):969978. doi:10.1007/s00280-020-04069-1.

19. Flaifel A, Xie W, Braun DA, et al. PD-L1 Expression and Clinical Outcomes to Cabozantinib, Everolimus, and Sunitinib in Patients with Metastatic Renal Cell Carcinoma: analysis of the Randomized Clinical Trials METEOR and CABOSUN. Clin Cancer Res. 2019;25(20):60806088. doi:10.1158/1078-0432.ccr-19-1135.

20. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228247. doi:10.1016/j.ejca.2008.10.026.

21. Miller TP, Fisher BT, Getz KD, et al. Unintended consequences of evolution of the Common Terminology Criteria for Adverse Events. Pediatr Blood Cancer. 2019;66(7):e27747. doi:10.1002/pbc.27747.

22. Song ZZ, Zhao LF, Zuo J, et al. Clinical Outcomes and Safety of Apatinib Mesylate in the Treatment of Advanced Non-Squamous Non-Small Cell Lung Cancer in Patients Who Progressed After Standard Therapy and Analysis of the KDR Gene Polymorphism. Onco Targets Ther. 2020;13:603613. doi:10.2147/ott.s222985.

23. Ma JT, Sun J, Sun L, et al. Efficacy and safety of apatinib in patients with advanced nonsmall cell lung cancer that failed prior chemotherapy or EGFR-TKIs: a pooled analysis. Medicine. 2018;97(35):e12083. doi:10.1097/md.0000000000012083.

24. Fang SC, Huang W, Zhang YM, Zhang HT, Xie WP. Hypertension as a predictive biomarker in patients with advanced non-small-cell lung cancer treated with apatinib. Onco Targets Ther. 2019;12:985992. doi:10.2147/ott.s189984.

25. Zhang D, Zhang C, Huang J, Guan Y, Guo Q. Clinical investigation of the efficacy and toxicity of apatinib (YN968D1) in stage III/IV non-small cell lung cancer after second-line chemotherapy treatment: a retrospective study. Thorac Cancer. 2018;9(12):17541762. doi:10.1111/1759-7714.12898.

26. Agemi Y, Shimokawa T, Sasaki J, et al. Prospective evaluation of the G8 screening tool for prognostication of survival in elderly patients with lung cancer: a single-institution study. PLoS One. 2019;14(1):e0210499. doi:10.1371/journal.pone.0210499.

27. Nadal E, Massuti B, Domine M, et al. Immunotherapy with checkpoint inhibitors in non-small cell lung cancer: insights from long-term survivors. Cancer Immunol Immunother. 2019;68(3):341352. doi:10.1007/s00262-019-02310-2.

28. Xie Q, Chen Z, Xia L, et al. Correlations of PD-L1 gene polymorphisms with susceptibility and prognosis in hepatocellular carcinoma in a Chinese Han population. Gene. 2018;674:188194. doi:10.1016/j.gene.2018.06.069.

29. Catalano C, da Silva Filho MI, Frank C, et al. Investigation of single and synergic effects of NLRC5 and PD-L1 variants on the risk of colorectal cancer. PLoS One. 2018;13(2):e0192385. doi:10.1371/journal.pone.0192385.

30. Hashemi M, Karami S, Sarabandi S, et al. Association between PD-1 and PD-L1 Polymorphisms and the Risk of Cancer: a Meta-Analysis of Case-Control Studies. Cancers. 2019;11(8):1150. doi:10.3390/cancers11081150.

31. Isobe K, Kakimoto A, Mikami T, et al. PD-L1 mRNA expression in EGFR-mutant lung adenocarcinoma. Oncol Rep. 2018;40(1):331338. doi:10.3892/or.2018.6442.

32. Du W, Zhu J, Chen Y, et al. Variant SNPs at the microRNA complementary site in the B7H1 3untranslated region increase the risk of nonsmall cell lung cancer. Mol Med Rep. 2017;16(3):26822690. doi:10.3892/mmr.2017.6902.

33. Zhang Z, Zhao Y, Lu F, et al. Multi-targeted tyrosine kinase inhibitors as third-line regimen in advanced non-small cell lung cancer: a network meta-analysis. Ann Transl Med. 2019;7(18):452. doi:10.21037/atm.2019.08.51.

34. Miyawaki E, Murakami H, Mori K, et al. PD-L1 expression and response to pembrolizumab in patients with EGFR-mutant non-small cell lung cancer. Jpn J Clin Oncol. 2020;50(5):617622. doi:10.1093/jjco/hyaa033.

35. Xu Y, Wan B, Chen X, et al. The association of PD-L1 expression with the efficacy of anti-PD-1/PD-L1 immunotherapy and survival of non-small cell lung cancer patients: a meta-analysis of randomized controlled trials. Transl Lung Cancer Res. 2019;8(4):413428. doi:10.21037/tlcr.2019.08.09.

36. Kim T, Cha YJ, Chang YS. Correlation of PD-L1 Expression Tested by 22C3 and SP263 in Non-Small Cell Lung Cancer and Its Prognostic Effect on EGFR Mutation-Positive Lung Adenocarcinoma. Tuberc Respir Dis. 2020;83(1):5160. doi:10.4046/trd.2019.0026.

37. Gennen K, Kasmann L, Taugner J, et al. Prognostic value of PD-L1 expression on tumor cells combined with CD8+ TIL density in patients with locally advanced non-small cell lung cancer treated with concurrent chemoradiotherapy. Radiat Oncol. 2020;15(1):5. doi:10.1186/s13014-019-1453-3.

38. Berntsson J, Eberhard J, Nodin B, et al. Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 in colorectal cancer: relationship with sidedness and prognosis. Oncoimmunology. 2018;7(8):e1465165. doi:10.1080/2162402x.2018.1465165.

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DALLAS June 21, 2021 Jean D. Wilson, M.D., an internationally known endocrinologist whose scientific discoveries led to profound insights into the mechanisms underlying sexual differentiation and led to now widely used treatments for prostate disease, died June 13. He was 88.

Wilson, seen here in 1962, graduated from UTSouthwestern Medical School in 1955 and joined the faculty in 1960, where he began his studies of testosterone.

Wilson, professor emeritus of internal medicine at UTSouthwestern, was largely responsible for current understanding of the mechanisms by which steroid hormones induce male sexual differentiation. He also was instrumental in identifying the scientific underpinnings of a widely prescribed class of drugs known as 5-alpha-reductase inhibitors which include finasteride (Proscar, Propecia) and dutasteride (Avodart) to treat enlarged prostate and balding in men.

Wilsons discovery of 5-alpha-reductase and the identification of dihydrotestosterone as the primary hormone associated with the growth of the prostate transformed our understanding of prostate gland growth and paved the way for new effective treatment of prostate disease, says Daniel K. Podolsky, M.D., president of UTSouthwestern. His findings led to the first medical therapy for benign prostatic hyperplasia, and also provided the basis for understanding of the mechanism underlying the differentiation of male and female genital development. His legacy will be found in the legions of patients who have benefited from the therapy made possible by his discoveries.

Wilson, seen in 1978, was a popular and highly sought-after attending physician on the wards of Parkland Memorial Hospital, valued for his vast expertise in endocrinology and medicine in general.

Jean Wilson was one of the most critical and helpful sources of information concerning the development of two important drugs we were developing at Merck the statins, for control of LDL cholesterol, and Proscar, for treatment of benign prostate enlargement. Wilson was always available to wrestle with problems that often arise in drug development. I needed expert friends in those early days, and probably still do, says P. Roy Vagelos, M.D., former chairman, president, and chief executive officer of Merck & Co. and now chair of the board of Regeneron Pharmaceuticals.

Wilsons research included the study of cholesterol metabolism and steroid hormone action. The UTSouthwestern Medical School graduate and former National Institutes of Health (NIH) researcher earned international prominence for his investigations of testosterone including its formation from cholesterol as well as its metabolism and action. His efforts elucidated disorders resulting from genetic defects that lead to disruption in sex hormone biosynthesis with corresponding alteration in development.

Collaborations at UTSouthwestern with David Russell, Ph.D., professor of molecular genetics, led to the cloning of the 5-alpha-reductase (5AR) gene, development of animal models for 5AR deficiency, and eventually the finding that a 5AR inhibitor blocked prostate growth, which resulted in clinical trials led by Claus Roehrborn, M.D., chair of urology. The human androgen receptor later was cloned in 1989, allowing Wilson and colleagues to identify the receptor as a transcription factor that could regulate both the receptor and 5AR expression in prostate cancer. Other scientists at UTSouthwestern expanded upon his research, identifying androgen involvement in virtually all aspects of prostate development, alternate mechanisms of androgen synthesis, and other forms of androgens related to castrate-resistant prostate cancer.

Among his numerous awards, Wilson received the Kober Medal from the Association of American Physicians (1999); the Fred Conrad Koch Award from The Endocrine Society (1993); Gregory Pincus Award from the Worcester Foundation for Experimental Biology (1992); Henry Dale Medal from the Society for Endocrinology (1991); Amory Prize from the American Academy of Arts and Sciences (1977); and the Eugene Fuller Award from the American Urological Association. He was elected as a member of the American Academy of Arts and Sciences (1982), the National Academy of Sciences (1983), and the National Academy of Medicine (1994) as well as the American Philosophical Society and served as president of the Endocrine Society, the American Society for Clinical Investigation, and the Association of American Physicians.

Wilson, seen in 1992, was elected as a member of the American Academy of Arts and Sciences (1982), the National Academy of Sciences (1983), and the National Academy of Medicine (1994).

Wilson, who had held the Charles Cameron Sprague Distinguished Chair of Biomedical Research, was known as a collaborative colleague and empathetic adviser to students and fellows. His approach with students and trainees was threefold find out what they want to do, encourage them to do it, and develop pathways to fulfill their goals, he said in an interview with The Journal of Clinical Investigation. He also noted that some of the most difficult students to counsel turned out to be late bloomers who really were worth an investment of time and effort.

At UTSouthwestern, he served as the first director of the Medical Scientist Training Program, and it was recently announced that the Physician Scientist Training Program in Internal Medicine would be known as the Jean Wilson Society. The Jean D. Wilson Center for Biomedical Research and The Jean D. Wilson, M.D. Award, which honor excellence in scientific research mentorship, are named in his honor. The center was established with support from Dr. Wilson and his sister, the late Dr. Margaret Sitton, to promote research in endocrinology, developmental biology, and genetics, along with the J.D. and Maggie E. Wilson Distinguished Chair in Biomedical Research. In addition, he served among editors of two landmark medical textbooks Williams Textbook of Endocrinology and Harrisons Principles of Internal Medicine and as editor for The Journal of Clinical Investigation, among other journals. He authored The Memoir of a Fortunate Man, which chronicles his life growing up in the Texas Panhandle through his rise to pioneering academic physician and researcher.

Jean was a popular and highly sought-after attending physician on the wards of Parkland Memorial Hospital, valued for his vast expertise in endocrinology and medicine in general, say Nobel Laureates Joseph Goldstein, M.D, chair of molecular genetics, and Michael Brown, M.D., director of the Erik Jonsson Center for Research in Molecular Genetics and Human Disease. He founded a diabetic foot clinic at Parkland and spent hours each week clipping toenails and treating ulcers on the feet of elderly diabetic patients. After long days on the wards, he would retire to his modest laboratory where he would spend half the night meticulously dissecting rabbit fetuses. Often, when we were just starting our careers, we would sit by his side while he dissected, receiving sage advice about our careers as physician-scientists and life in general. Later, he extended his fatherly role to generations of M.D./Ph.D. students when he became the founding director of our M.D./Ph.D. program.

He had a rich life outside of the Medical Center as well. An avid opera buff, Wilson collected antique gramophones that could play every type of recording that had ever been produced. His extensive collection of 3,500 old 78-rpm operatic recordings included a 1917 disc of Enrico Caruso singing songs of Irving Berlin the only record that Caruso ever recorded in English, they note.

An avid opera buff, Wilson, seen in 2019, collected antique gramophones. His extensive collection of 3,500 old 78-rpm operatic recordings included a 1917 disc of Enrico Caruso singing songs of Irving Berlin the only record that Caruso ever recorded in English.

He took memorable trips to places like the North Pole, Antarctica, the Galapagos Islands, and the Easter Islands. He often incorporated science into his trips, visiting the Kangaroo Island in Australia to study sexual development in wallabies, and to Kenya to biopsy the phallus of the spotted hyena. Fearless in the pursuit of knowledge, he performed a rectal examination on a lion to estimate the size of the prostate, Goldstein and Brown say. A dedicated bird watcher, he traveled the world to many exotic places, hoping to spot that rare bird. But in the end, the rarest of that rare bird was Jean Wilson himself.

Born in Wellington, Texas, in 1932, Wilson obtained an undergraduate degree in chemistry from UT Austin and graduated from UTSouthwestern Medical School in 1955. As a student, he studied the control of urinary acid secretion by adrenal hormones, and as a resident, he investigated cholesterol metabolism. After residency, he spent two years at the NIH, where he studied ethanolamine biosynthesis. He joined the UTSouthwestern faculty in 1960 where he began his studies of testosterone, and worked in 1970 at Cambridge University. In all, he spent 60 years at UTSouthwestern and was named professor emeritus of UTSouthwesterns storied internal medicine department in 2011.

Jean Wilson leaves us with a remarkable legacy a quintessential physician-scientist whose scholarship both inspires and continues to serve as a foundation for new advances, says Podolsky, also professor of internal medicine.

In a career spanning six decades at UTSouthwestern, Dr. Jean Wilsons discoveries included:

Cholesterol metabolism

Dr. Wilson developed methods for quantifying cholesterol synthesis, absorption, degradation, and excretion in lab animals. Together, these analytical methods served as tools for understanding the feedback control of cholesterol synthesis and turnover. In addition, Dr. Wilson demonstrated that plasma cholesterol is synthesized in the intestinal wall and liver, findings that helped researchers define the contributions of diet and endogenous synthesis to cholesterol turnover in humans and other primates.

Male androgens

Concurrently, Dr. Wilson studied the action of male androgens, focusing on testosterone and its metabolite, dihydrotestosterone. Starting with a collaboration with his postdoctoral fellow, Nicholas Bruchovsky, in 1966, the researchers discovered that testosterone is converted inside prostate cells into dihydrotestosterone, a more potent androgen that is responsible for most of male sexual maturation and male sexual function. Dr. Wilson and his colleagues later showed that mutations that impair either the synthesis of testosterone, the conversion of testosterone to dihydrotestosterone, or the function of this metabolites receptor protein are the most common cause of birth defects associated with incomplete development of the male urogenital tract, affecting about four in every 1,000 boys. Cloning these responsible genes eventually allowed researchers to identify asymptomatic carriers of these mutations.

Dihydrotestosterone

Dr. Wilson also discovered that excess dihydrotestosterone is responsible for benign prostatic hyperplasia (BPH), or prostate enlargement, a condition that affects about 210 million men worldwide. Dihydrotestosterone is responsible for prostate growth in all male mammals, but in humans and dogs, prostate growth continues throughout life. Wilson and his colleagues showed that local excess of this potent androgen leads to prostate overgrowth. By curbing its production by inhibiting 5a-reductase, the enzyme that converts testosterone to dihydrotestosterone, they were able to prevent BPH in dog models of this condition. These findings have been developed into multiple 5a-reductase-inhibiting pharmaceuticals to treat this condition in human patients.

Brown, a Regental professor and director of the Erik Jonsson Center for Research in Molecular Genetics and Human Disease, holds The W.A. (Monty) Moncrief Distinguished Chair in Cholesterol and Arteriosclerosis Research, and the Paul J. Thomas Chair in Medicine.

Goldstein, a Regental professor and chair of molecular genetics, holds the Julie and Louis A. Beecherl, Jr. Distinguished Chair in Biomedical Research, and the Paul J. Thomas Chair in Medicine.

Podolsky holds the Philip OBryan Montgomery, Jr., M.D. Distinguished Presidential Chair in Academic Administration, and the Doris and Bryan Wildenthal Distinguished Chair in Medical Science.

Russell holds the Eugene McDermott Distinguished Chair in Molecular Genetics.

About UTSouthwestern Medical Center

UTSouthwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institutions faculty has received six Nobel Prizes, and includes 24 members of the National Academy of Sciences, 16 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,800 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UTSouthwestern physicians provide care in about 80 specialties to more than 117,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 3 million outpatient visits a year.

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In Memoriam: Jean Wilson, M.D., made scientific discoveries that led to effective prostate treatments, insights into sexual differentiation - UT...

CAMBRIDGE, Mass. and ROSTOCK, Germany and BERLIN, June 22, 2021 (GLOBE NEWSWIRE) -- Centogene N.V. (Nasdaq: CNTG), a commercial-stage company focused on generating data-driven insights to diagnose, understand, and treat rare diseases, will hold its first Virtual Investor Event, presented by its newly formed executive team.

Andrin Oswald, M.D., Chief Executive Officer at CENTOGENE, stated, Over the past 15 years, CENTOGENE has built a unique expertise and has become the leading data-driven insights provider purely focused on rare genetic diseases. We are now embarking on our next growth phase enabling the cure of 100 rare diseases within the next 10 years. This represents the potential to significantly contribute to reducing the burden of rare diseases.

This next chapter is powered by our unparalleled genomics knowledge, the worlds largest rare disease-centric Bio/Databank, global footprint, and strong established network of physicians, partners, and patients. Together with our AI and multiomic tools, this puts us at the focal point of precision medicine for genetically linked rare diseases driven by the ability to unlock the complexities of patients biology to diagnose, understand, and treat these diseases effectively. As the rare disease market is vast and often overlooked, and as our capabilities will contribute significantly to the sector, we believe that this new focus will offer substantial possibilities for value creation.

Diagnose. Understand. Treat.

Founded in 2006, CENTOGENE has long been known for its expertise in the field of rare disease genetics helping over 600,000 patients and building a rare disease-centric Bio/Databank. Aspiring to reduce the heavy burden of rare diseases through data-driven insights, the Company has established itself as the leading partner of choice for patients, physicians, and pharma partners.

At the Virtual Investor Event, the Company will announce its strategic multi-pronged approach to diagnose, understand, and treat rare diseases by finding, connecting, and investigating patients and their biology from around the world.

Strategic Priorities to Accelerate the Discovery, Development, and Access to Orphan Drugs

While the Company continues to drive targeted innovation, its priorities remain the same: investing and building its Diagnostics and Pharma segments to transform the science of clinical and genetic data into medical solutions for rare disease patients.

In both of CENTOGENEs core business segments, the Company has established unique positioning and has laid the foundation for growth and impact expected in the near-, mid-, and long-term. Leveraging its rare disease expertise while expanding technology capabilities, CENTOGENE is confident about its path to enabling the cure of 100 rare diseases.

Register for the VirtualInvestorEvent

The Company will be hosting the Virtual Investor Event today, June 22, 2021, at 9:00 a.m. - 11:00 a.m. EDT / 3:00 p.m. - 5:00 p.m. CEST. To register visit: https://www.centogene.com/virtual-investor-event.html

Participants may also access the conference call by dialing U.S. toll free +1 855 979 6654 or U.K. +44 (0) 800 640 6441 up to 10 minutes prior to the start of the call and by providing the conference ID number 182810. Other participant dial-in numbers can be found on the events registration page.

About CENTOGENE

CENTOGENE engages in diagnosis and research around rare diseases transforming real-world clinical, genetic, and multiomic data to diagnose, understand, and treat rare diseases. Our goal is to bring rationality to treatment decisions and to accelerate the development of new orphan drugs by using our extensive rare disease knowledge and data. CENTOGENE has developed a global proprietary rare disease platform based on our real-world data repository with over 3.9 billion weighted data points from approximately 600,000 patients representing over 120 different countries as of December 31, 2020.

The Companys platform includes epidemiologic, phenotypic, and genetic data that reflects a global population, as well as a biobank of patients blood samples and cell cultures. CENTOGENE believes this represents the only platform focused on comprehensive analysis of multi-level data to improve the understanding of rare hereditary diseases. It allows for better identification and stratification of patients and their underlying diseases to enable and accelerate discovery, development, and access to orphan drugs. As of December 31, 2020, the Company collaborated with over 30 pharmaceutical partners.

Important Notice and Disclaimer

This press release contains statements that constitute forward-looking statements as that term is defined in the United States Private Securities Litigation Reform Act of 1995, including statements that express the Companys opinions, expectations, beliefs, plans, objectives, assumptions, or projections regarding future events or future results, in contrast with statements that reflect historical facts. Examples include discussion of our strategies, financing plans, growth opportunities, and market growth. In some cases, you can identify such forward-looking statements by terminology such as anticipate, intend, believe, estimate, plan, seek, project or expect, may, will, would, could, or should, the negative of these terms or similar expressions. Forward-looking statements are based on managements current beliefs and assumptions and on information currently available to the Company. However, these forward- looking statements are not a guarantee of our performance, and you should not place undue reliance on such statements. Forward-looking statements are subject to many risks, uncertainties, and other variable circumstances, such as negative worldwide economic conditions and ongoing instability and volatility in the worldwide financial markets, the effects of the COVID-19 pandemic on our business and results of operations, possible changes in current and proposed legislation, regulations and governmental policies, pressures from increasing competition and consolidation in our industry, the expense and uncertainty of regulatory approval, including from the U.S. Food and Drug Administration, our reliance on third parties and collaboration partners, including our ability to manage growth and enter into new client relationships, our dependency on the rare disease industry, our ability to manage international expansion, our reliance on key personnel, our reliance on intellectual property protection, fluctuations of our operating results due to the effect of exchange rates, or other factors. Such risks and uncertainties may cause the statements to be inaccurate and readers are cautioned not to place undue reliance on such statements. Many of these risks are outside of the Companys control and could cause its actual results to differ materially from those it thought would occur. The forward-looking statements included in this press release are made only as of the date hereof. The Company does not undertake, and specifically declines, any obligation to update any such statements or to publicly announce the results of any revisions to any such statements to reflect future events or developments, except as required by law.

For further information, please refer to the Risk Factors section in our Annual Report for the year ended December 31, 2020, on Form 20-F filed with the SEC on April 15, 2021, and other reports and documents furnished to or filed with the U.S. Securities and Exchange Commission (SEC). You may get these documents by visiting EDGAR on the SEC website at http://www.sec.gov.

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CENTOGENE Sets Mission to Enable the Cure of 100 Rare Diseases Within the Next 10 Years Highlights strategic priorities to lead data-driven insights...

Vanderbilt University Medical Center will participate in a new federal initiative aimed at improving the use of polygenic risk scores (PRS) to predict complex diseases in diverse populations.

This week the National Institutes of Health (NIH) announced it will fund grants totaling $38 million over five years to establish and support a PRS Diversity Consortium. VUMC researchers will co-lead two of the consortiums six PRS centers.

Polygenic risk scores provide a genetic estimate of disease risk. Because most PRS were developed using data from European ancestry study samples, they perform poorly in predicting disease risk when applied to other racial and ethnic groups.

Nancy Cox, PhD, the Mary Phillips Edmonds Gray Professor of Genetics and director of the Vanderbilt Genetics Institute, will co-direct one of the centers with Yun Li, PhD, at the University of North Carolina at Chapel Hill, and Alexander Reiner, MD, at the University of Washington in Seattle.

Maggie Ng, PhD, associate professor of Medicine in the Division of Genetic Medicine at VUMC, will co-lead another center with Josep Mercader, PhD, and Alisa Manning, PhD, at the Broad Institute of MIT and Harvard in Cambridge, Massachusetts.

We focus largely on quantitative biomarkers of disease that are commonly measured for understanding disease risks and progression, mostly blood-based measures and those related to inflammatory biology, Cox said.

We also have a focus on developing and testing PRS in diverse populations, she added, because disproportionate numbers of people from minority populations in the United States fall outside the normal reference ranges.

The VUMC-Broad Institute collaboration will work on improving the PRS prediction of diabetes and its complications, which Ng called one of the greatest global health challenges of the 21st century.

The centers multi-disciplinary team will aggregate and analyze data from genome-wide association studies of more than 1.8 million individuals with type 1 and type 2 diabetes, gestational diabetes and glycemia-related complications, 35% of whom are non-European.

VUMCs biobank, called BioVU, will be an important resource because it contains a large number of genome-wide genotypes from diverse samples including African Americans and Hispanics.

VUMC also maintains for research purposes electronic health records of people who donated blood and other biological samples to BioVU, but from which all information that could identify them has been deleted.

These tools and data will help researchers improve the PRS prediction of diabetes and its progression in a setting where dramatic racial, ethnic and socioeconomic disparities exist, Ng said.

Improved prediction of diabetes, in turn, can inform more efficient and targeted preventive strategies within health care systems and across ethnically diverse populations and advance precision care, she said.

The National Human Genome Research Institute (NHGRI), part of NIH, will fund five awards for $33 million, while the National Cancer Institute will fund one award for $5 million.

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VUMC joins national effort to improve disease prediction in diverse populations - Johnson City Press (subscription)

June is Migraine and Headache Awareness Month. Nearly one in four U.S. households has someone living with migraine. It is the number two cause of disability in the world, according to a study in the Journal of Headache and Pain, yet some people still dont recognize how debilitating migraine can be.

Abby Metzler, MD, an assistant professor of neurology at the University of Minnesota Medical School and a neurologist with M Health Fairview, explains migraine diagnosis, living with migraine and current treatment and prevention options.

Q: What are the symptoms of a migraine?Dr. Metzler: A migraine attack is a headache and other debilitating symptoms that lasts at least four hours and can go up to 72 hours, if untreated. The headache is usually pulsing or throbbing. People typically think of the headache as being on one side of the head, which is common, but it is also common to have a migraine attack that affects both sides. In addition to headache, migraine attacks also cause nausea or vomiting, or sensitivity to light and sound. A migraine attack affects someones ability to think and function and worsens with routine physical activity, like going up and down stairs.

It is not a one-time event, and it stereotypically happens the same way each time. By criteria, it has to happen at least five times before you can officially be diagnosed with the disorder, migraine.

About one-third of people with migraine have migraine with aura. Aura is a neurological disturbance that leads to headache and other symptoms. This can include seeing zig-zag lines, flashing lights, blind spots, numbness/tingling or more.

Q: How can someone differentiate between a headache caused by migraine or something like a stroke or brain tumor?Dr. Metzler: There are several features I look for when evaluating someone for secondary causes of headache or headaches that are not caused by a headache disorder itself. I like the acronym SNOOP4 to review signs that might require more investigation. SNOOP4 stands for:

Systemic signs fever, weight loss, history of cancer

Neurological exam abnormalities facial drooping, weakness, numbness or other neurological sign that isnt typical for the person

Older than 50 developing new headaches after age 50

Onset is acute pain level goes from zero to 10 in less than a minute. Someone experiencing a headache that comes all of a sudden and is very severe should go to the emergency department.

Pattern change change in frequency, intensity or symptoms usually associated with someones headaches

Progressive getting worse despite treating it how they normally do

Positional headache only when standing up or laying down

Precipitated by valsalva only happens with bearing down, coughing or sneezing

Q: How can someone alter the way they live to help reduce migraine attacks?Dr. Metzler: I use another acronym, SEEDS, for a lifestyle management strategy for people with migraine. It is important to note that people with migraine do not cause their migraine attacks, which are instead caused by the genetic neurologic disorder of migraine. These are some actions to help reduce the number of triggers, which can help to reduce the number of attacks, sometimes in combination with medications.

Sleep routine Go to bed and wake up at the same time.

Exercise Be active more days than not. People with headaches who exercise do better than people who dont.

Eating Eat healthy. There is not a specific recommended diet, but making healthier choices in general and not skipping meals will produce better results.

Diary of symptoms Keep track of when you have headaches and when they affect your functioning. This will help you and your doctor determine the best treatment plan.

Stress management Stress is the most commonly reported trigger for migraine. It is important to find ways to step back and prioritize yourself.

Q: Are there things people can do to prevent getting migraine?Dr. Metzler: Not really. Migraine is a genetic, neurologic disorder that is passed down in families. Research studies have identified dozens of genes in different families that cause the propensity for migraine attacks. There is about a 50/50 chance that the child of someone with migraine will also have migraine. However, the parent and child may be affected differently. For instance, the parent may have severe migraine disease and their child may have rare attacks. It is likely a combination of genetics and environment.

Q: What are some current treatment options for migraine?Dr. Metzler: For migraine treatment, there are many different acute and preventative options. The FDA has also approved a number of newer treatments for migraine. Your doctor can determine whether you are a candidate for a newer treatment.

CGRP (calcitonin gene-related peptide) inhibitors are approved for migraine prevention. They include erenumab, fremanezumab, galcanezumab and eptinezumab. They are monoclonal antibodies and are administered via monthly injections, except eptinezumab which is administered via an infusion every three months.

Botulinum Toxin (Botox) injections are also used as a preventative treatment for chronic migraine. People who use this method receive a set of injections over the head, neck, and shoulders every 12 weeks.

Rimegepant and ubrogepant are CGRP inhibitor pills that treat migraine. As soon as someone realizes they have a migraine attack, they take a pill for acute treatment, or they may take a pill every other day for prevention.

Lasmiditan is a serotonin agonist pill that treats migraine when it occurs. It may be a good option for patients who cannot take triptan medications.

None of these medications are available or should be taken without the consultation of a doctor.

Abby Metzler, MD, is an assistant professor of neurology at the University of Minnesota Medical School and a neurologist with M Health Fairview. She treats patients living with headaches at M Health Fairview Clinics and Surgery Center Minneapolis in the Neurology Clinic. She is board-certified by the American Board of Psychiatry & Neurology.

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About Talking...with U of MTalking...with U of M is a resource whereby University of Minnesota faculty answer questions on current and other topics of general interest. Feel free to republish this content. If you would like to schedule an interview with the faculty member or have topics youd like the University of Minnesota to explore for future Talking...with U of M, please contact University Public Relations at unews@umn.edu.

About the University of Minnesota Medical SchoolThe University of Minnesota Medical School is at the forefront of learning and discovery, transforming medical care and educating the next generation of physicians. Our graduates and faculty produce high-impact biomedical research and advance the practice of medicine. We acknowledge that the U of M Medical School, both the Twin Cities campus and Duluth campus, is located on traditional, ancestral and contemporary lands of the Dakota and the Ojibwe, and scores of other Indigenous people, and we affirm our commitment to tribal communities and their sovereignty as we seek to improve and strengthen our relations with tribal nations. For more information about the U of M Medical School, please visit med.umn.edu.

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Talking Migraine with the U of M - UMN News

Our results suggest that common genes and signaling pathways are involved in PTSD and migraine and this might explain why PTSD and migraine can cooccur frequently, said senior author on the study, Divya Mehta, PhD, of the Queensland University of Technology. This might further imply that common environmental risk factors for both PTSD and migraine might be acting on these genes.2

The study observed 6 pairs of monozygotic (MZ) twins discordant for PTSD and 15 pairs of MZ twins discordant for migraine. PTSD was measured through phone interviews conducted by an experienced interviewer using structured questions and DSM-IV criteria. All 6 pairs of twins were identified as having experienced a PTSD-qualifying potentially traumatic event as per the DSM-IV criteria. Migraine was assessed using the International Headache Society (IHS) diagnostic criteria, the International Classification of Headache Disorders, ICHD-3, together with a diagnosis of migraine with or without aura. Pairs of twins discordant for migraine with aura were chosen for the study.

Blood samples were taken from all participants. Association between DNA methylation and PTSD status was tested using linear mixed effects models with age, sex, and cell counts as covariates. Using the same study design as the PTSD sample of twins, the 15 pairs of MZ twins discordant for migraine were tested for association of methylation at genetic loci that overlap between PTSD and migraine using varied analyses.

At the epigenome-wide level, researchers assessed how many of the 1036 genes associated with PTSD overlapped with those significantly associated with migraine in the discordant migraine MZ twins.

We identified DAPK2 and TM6SF2 as two of the top overlapping genes between the two disorders. DAPK2 is a calmodulin-regulated protein kinase, it has been implicated in the intracellular degradation process essential for adaptation to metabolic stress (autophagy). TM6SF2 is associated with cardiovascular disease and plays a role in oxidative stress. These findings suggest that epigenetic changes in response to different types of stress may mediate stress phenotypes, said the studys authors.1

The findings could form the basis for new treatments. Epigenetic changes offer an excellent drug target, as they can often be reversed.

These results may have implications for treatments, as one medicine or therapy might only be effective for a single disorder, said Mehta. For co-occurring disorders such as PTSD and migraine, once we know which common genes are implicated in both disorders, we can develop new therapeutics to target these, thereby reducing symptoms and curing both.

References

1. Bainomugisa CK, Sutherland H, Parker R, et al. Using monozygotic twins to dissect common genes in posttraumatic stress disorder and migraine. Frontiers in Neuroscience. June 22, 2021. https://doi.org/10.3389/fnins.2021.678350

2. Frontiers. Twin study is first to reveal common genetic risk factors for PTSD and migraine.News release. June 22, 2021. https://blog.frontiersin.org/2021/06/22/neuroscience-twins-genes-risk-ptsd-migraine/

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Are Migraines and PTSD Linked? - Psychiatric Times