Category Archives: Genetic medicine

They couldn't explain why those afflicted, often in the same family, had recurring fevers, abdominal pain, troublesome rashes and muscle aches. Known as familial Mediterranean fever, the disease often went undiagnosed for years, and it was sometimes fatal.

A similar, but unrelated, mystery fever was initially thought to affect families with Scottish and Irish heritage.

"The pain I felt back then, it moved around. One week the pain was in my leg, and the next week my arm would hurt instead," said Victoria Marklund, 47, a Swedish woman who suffered from TRAPS, or tumor necrosis factor receptor-associated periodic syndrome, a disease first identified in a family of Irish and Scottish descent living in the UK city of Nottingham in 1982.

Her father and grandfather died prematurely from kidney complications, which were likely a consequence of the undiagnosed disorder.

Marklund has now received an effective treatment and lives symptom-free -- largely thanks to the work of one US physician and health researcher, Dr. Dan Kastner, a distinguished investigator at the National Institutes of Health who serves as scientific director of the National Human Genome Research Institute.

"What Dr. Kastner has accomplished is absolutely groundbreaking. The concept of autoinflammatory disorders didn't exist before he identified the cause behind a number of them," said Olle Kmpe, a professor of clinical endocrinology at Karolinska Institutet in Stockholm who is a member of The Royal Swedish Academy of Sciences and chair of the Prize Committee. The academy also selects Nobel laureates.

"His discoveries have taught us a great deal about the immune system and its functions, contributing to effective treatments that reduce the symptoms of disease from which patients previously suffered enormously," Kmpe added.

Breakthrough

Kastner first came across familial Mediterranean fever in a patient with recurring arthritis and high fevers he treated as a rheumatology fellow just months into his first job at the NIH in Bethesda, Maryland, in 1985. That chance diagnosis set him on a 12-year journey to find the gene -- or genes -- responsible for the disease.

"It was known that familial Mediterranean fever was a genetic disease. It was known that it was recessively inherited, but no one knew what the gene was, or even the chromosome," he said.

He traveled to Israel, where he took blood samples from 50 families with familial Mediterranean fever.

It took Kastner seven years to locate the mutation to chromosome 16. It took another five years -- in 1997 -- for Kastner and his team to find the mutated gene itself -- one misprint in a genetic code comprised of 3 billion letters.

After this breakthrough, he stayed at NIH, where he studied undiagnosed patients with similar symptoms. He identified 16 autoinflammatory genetic disorders and found effective treatments for at least 12 of them, establishing a whole new field of medicine.

Now that the full human genome has been mapped, the process of detecting the genetic root of such disorders is quicker, and greater numbers of patients with these rare, unexplained diseases are being helped as a result of Kastner's work.

All-nighters

There are few images in science more iconic than the DNA double helix structure, discovered in 1953 by James Watson and Francis Crick, two years after Kastner was born. As a seventh grader, he once created a version of the twisted ladder shape using jelly beans and pipe cleaners for a science fair.

His work to identify the gene that caused familial Mediterranean fever had its own element of competition. In the summer of 1997, to beat a rival team led by French researchers, Kastner took a last-minute flight from Bethesda, Maryland, where the NIH is based, to Boston to submit his manuscript detailing the gene mutation that caused familial Mediterranean fever by hand to the journal Cell on a Friday afternoon.

These were the days before papers could be submitted with the click of a mouse. He hoped to publish his work first. Ultimately, the two teams published their papers simultaneously in different journals -- both fortunately arriving at the same finding.

"I love that type of thing," he said. "We still have races to the finish, and there's nothing like a good week of all-nighters."

Kastner had discovered that the gene involved in familial Mediterranean fever produces a protein called pyrin. Normally this helps to activate our innate immune system -- our first line of defense to fight bacteria and viruses.

In this case, however, pyrin made the innate immune system become overactive, resulting in fever, pain and joint inflammation. He went on to study patients with similar and more devastating symptoms -- identifying TRAPS and many more rare diseases.

Transforming lives

What has motivated Kastner for five decades is how his work decoding the genetics of inflammation can inform new treatments and ultimately transform patients' lives.

"There's nothing more gratifying in life and nothing more satisfying scientifically," he said. He plans to step down from his role as scientific director at the NIH in the next few months and then focus his efforts on his clinic, where he has over 3,000 patients enrolled and "find yet more disease genes, understand how they work, and develop new treatments."

"Of course, one can never know how long that will last, but I love doing it, and will continue as long as I can."

In more recent work beginning in 2014, Kastner identified and pioneered treatment for a severely debilitating genetic disorder known as DADA2, short for deficiency of the enzyme ADA2 (adenosine deaminase 2), which can cause recurring fevers and strokes starting in childhood. His research has radically improved the life of the daughter of Dr. Chip Chambers.

"She's now at college and the improvement in her quality of life has been dramatic."

Similarly, TRAPS survivor Marklund suffered for years before her diagnosis at the age of 38. Her nephews, who both have TRAPS but have been given medicine from an early age, don't feel the effects of the disease at all, she told The Royal Swedish Academy Of Sciences.

"I doubted many times that anyone would ever figure out what I was suffering from. So now it feels fantastic, to be told what it was, to understand the cause of the disease and that there is medicine that helps."

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Mysterious untreatable fevers once devastated whole families. This doctor discovered what caused them - CNN

January was a busy month for the US Food and Drug Administrations precision medicine efforts, as the agency produced guidance on ASO drugs for patients with debilitating or life-threatening genetic disorders and guidance on manufacturing considerations for certain cellular and gene therapy products during the COVID-19 pandemic.

The agency first issued a draft guidance to facilitate the development of individualized antisense oligonucleotide (ASO) drugs for patients with severely debilitating or life-threatening genetic disorders (ASO Guidance). The Food and Drug Administration (FDA) also issued a guidance, with immediate effect, on manufacturing considerations for licensed and investigational cellular and gene therapy products during the COVID-19 public health emergency (Manufacturing Guidance). Sponsors investigating or marketing these products should pay special attention to the discussion in these documents, as FDA outlines its approach to COVID-19 and development considerations with respect to these personalized therapies.

Manufacturing Guidance

The Manufacturing Guidance supplements FDAs June 2020 guidance on Good Manufacturing Practice Considerations for Responding to COVID-19 Infection in Employees in Drug and Biological Products Manufacturing. However, because cell and gene therapy (CGT) manufacturers may face special challenges, FDA recommends that CGT manufacturers perform risk assessments to identify, evaluate, and mitigate factors that may allow for the transmission of SARS-CoV-2 through CGT products. Any plans should take into account FDAs view that allogeneic products may be associated with a higher risk of infection compared to autologous products.

FDA specifically recommends the following:

As always, any adopted risk assessment and mitigation strategies must be documented and approved by the manufacturers quality unit, should include scientific justification and literature references, and should be submitted to FDA.

ASO Guidance

Turning away from the current COVID-19 crisis, FDA indicated that it is also looking ahead to the continued advancement of personalized therapies, issuing the ASO Guidance to assist sponsor investigators in the development of individualized ASO products for severely debilitating or life-threatening genetic diseases that are tailored to a patients specific genetic variant. As noted by FDA, the ASO Guidance is targeted to academic investigators, who may be less familiar with FDAs requirements and less experienced in interacting with FDA.

While the specific impetus for this guidance is unclear, assumedly FDA is receiving more inquiries regarding individualized ASO drugs from investigators, patients, or those acting on their behalf. Regardless of the reason, healthcare institutions where ASO products are used should familiarize themselves with FDAs requirements and processes to ensure that any use of an investigational ASO product accords with FDAs regulations. It will also be important that manufacturers supporting the use of ASO products or that later intend to work with ASO product investigators ensure that programs comply with FDAs regulations via contractual agreements and, as appropriate, due diligence.

For these programs, FDA recommends the following:

The ASO Guidance is likely a first step in the development of individualized therapies. As stated by FDA, the agency is optimistic that development of [ASO] individualized drug products may spur gene sequencing that leads to the development of additional individualized drug products. Accordingly, through the ASO Guidance, FDA aims to determine the most effective and efficient way to bring personalized drugs to patients, while ensuring the right risk-benefit balance.

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FDA Issues More Guidance on Gene and Cell Therapy Products - Lexology

As part of the federal governmentsinvestment in domestic vaccine capability, a Vancouver company is taking their $25.1 million allotment to build a massive manufacturing facility in the Lower Mainland.

South Vancouver-basedPrecision Nanosystemsis building a $50.2 million biomanufacturing centre that could produce up to 240 million doses of vaccine every year in the 40,000 square foot facility. It's still assessing possible locations.

Its estimated completion date is March 2023, but the companys CEO says the investment is important on a number of levels.

"It's an investment in pandemic preparedness, an investment in the future, an investment in these critical technologies that are really the technologies of the future, said James Taylor in a Zoom interview. What were focussed on is the medium- to long-term pandemic responsiveness as well as developing capabilities and capacity around genetic medicine itself, so our facility will be able to utilize for programs that are involved in cancer, infectious diseases, rare diseases.

The same kind of messenger RNA technology that companies like Pfizer-BioNTech and Moderna have developed to quickly create and manufacture their successful COVID-19 vaccines is the same idea behind many local companies like Precision Nanosystems. Many members of the scientific community believe such genetic medicines that treat diseases at the molecular level are on the cusp of revolutionizing medicine.

"As long as you know how to create those instructions -- that genetic code you need to convince your body to create that target -- you can design an mRNA vaccine against any antigen," said Nicole Basta, an associate professor of epidemiology at McGill told the Canadian Press.

Vancouver-based Acuitas Therapeutics developed a lipid nanoparticle to protect the delicate messenger RNA strands that can be broken down by the body. https://www.ctvnews.ca/health/coronavirus/a-canadian-company-helped-make-one-of-the-most-promising-vaccine-candidates-1.5193860

Taylor described the Lower Mainland as a global hub in nano-medicines, pointing out the growing industry is deeply intertwined with researchers, scientists and experts working across borders on shared projects; Precision Nanosystems alone works with more than 160 other companies around the world.

This past a year has really shone a light on the importance of science and technology to solve deep problems globally, he said. It's important for us, as Canadians, to be strong participants in the development and innovation.

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Vaccine Production in BC's Future - AM 1150 (iHeartRadio)

Bioinformatics is the field mainly involving molecular biology, genetics, mathematics, statistics, and computer science. The bioinformatics services include analysis of the data that can range from processing sequencing reads from instrument to data aggregation and mining data samples. Bioinformatics services can help biologists to understand the biological process with a computational intensive technique for machine learning algorithms, pattern recognition, data mining and visualization.

Bioinformatics tools can help to compare genomic and genetic data and understand evolutionary aspects of molecular biology. Bioinformatics services are finding wide application in chemoinformatics, genomics, metabolomics, RNA-seq analysis, and drug design. The database is an important part for bioinformatics research and application to cover various information types including molecular structure, protein and DNA sequences, and phenotypes in bioinformatics services.

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Bioinformatics Services Market: Notable Highlights

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Some of the most prominent competitors operating in the competitive landscape of global bioinformatics services market include

Bioinformatics Services Market Dynamics

Bioinformatics Services Finding Wide Application in Personalized Medicine Discovery

With the increasing prevalence of various diseases, new treatments and drugs are being discovered and developed. Extensive molecular biological data on patients is being included on a large scale in diagnosis and treatment. Bioinformatics services is fundamental to precision medicine as developing personalized medicine depends on accessing genetic and molecular data. In recent years, the majority of the molecularly targeted drugs have been developed based on the detected gene mutation.

Next-gen sequencing in bioinformatics services is emerging as an important tool in genomic analysis and developing personalized medicine. Next-gen sequencing along with microarrays in bioinformatics services have also paved the way for precision medicine in oncology. Meanwhile, increasing availability and decreasing the cost of next-gen sequencing is allowing worldwide cancer centers to offer next-gen sequencing based personalized oncology for clinical practice while suggesting specific medicine and treatment.

Increasing Initiatives by Governments and Private Organizations in Bioinformatics Services

With increasing application of new technologies in life science, governments and organizations across various countries are investing in the new technologies and in research and development activities in bioinformatics services. According to the Global Alliance for Genomics and Health (GA4GH), around 60 million genomes are likely to be sequenced by 2025. Moreover, with the presence of national clinical genomic initiatives worldwide, the generation of genomic data in healthcare is expected to outpace that in research in the coming years. Governments across countries are increasingly investing in the biotechnology and bioinformatics services to effectively implement new technologies and support genomic and epidemiological research.

Countries such as the US, UK, Australia, France, Japan, Saudi Arabia, Qatar, Denmark are developing new strategies for projects focusing on cancer and rare diseases, along with the use of sequencing services and genomic data. New research activities are also being conducted for application of bioinformatics services in biodefense. The Mid-Atlantic Microbiome Meet-up (M3) is focusing on the use of next-generation sequencing technologies and recent advances in biodefense, especially related to infectious diseases, and also using metagenomic methods for detection.

Shortage of Skilled Workforce and High Cost Hampering the Bioinformatics Services Market Growth

Although bioinformatics services is emerging as an important part of research in life science, lack of skills and knowledge in bioinformatics is hindering its growth. With the technological and process advancements in biotechnology, it has become imperative that bioinformatics techniques are performed by skilled personnel. However, the need for heavy investment in tool upgradation and installation training is impeding the growth of bioinformatics services. Owing to this there is a lack of skilled manpower in bioinformatics services who can adapt to the high-end bioinformatics techniques and processes.

Moreover, the lack of skilled professionals in bioinformatics services is also hampering the growth of clinical laboratories as they are focusing to automate processes. However, in recent years, governments along with healthcare institutions are focusing on strategies to provide new courses in bioinformatics as it holds a big promise in solving many health related and environmental issues.

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Bioinformatics Services Market Segmentation

Based on the type, the bioinformatics services market is segmented into

On the basis of application, the bioinformatics services market segment includes

Based on the specialty, the bioinformatics services market is segmented into

Based on the end-user, the bioinformatics services market segment includes

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Bioinformatics Services Market | Know the Latest Innovations and Future Market Scope - BioSpace

Jan. 29, 2021 12:00 UTC

Program to screen for congenital, monogenic hearing loss in children diagnosed with auditory neuropathy

BOSTON--(BUSINESS WIRE)-- Decibel Therapeutics, a clinical-stage biotechnology company dedicated to discovering and developing transformative treatments to restore and improve hearing and balance, today announced a partnership with Invitae, a leading medical genetics company, to launch AmplifyTM, a no-charge genetic testing program to screen for the genetic cause of congenital hearing loss in children diagnosed with auditory neuropathy.

We are pleased to collaborate with Invitae to introduce AmplifyTM, which is designed to bring patients one step closer to molecular diagnosis and clinical management of auditory neuropathy, a disorder that affects approximately 10 percent of children who are born with hearing loss, said Jonathon Whitton, Au.D., Ph.D., Vice President of Clinical Research at Decibel. This program seeks to provide much-needed answers to patients and families of patients who experience congenital, monogenic hearing loss. We hope that AmplifyTM will provide those patients with a better understanding of their diagnosis and their treatment options.

Auditory neuropathy is a hearing disorder in which the cochlea, the hearing organ located in the inner ear, receives sound normally, yet the transmission of sound to the brain is interrupted. The most common genetic cause of auditory neuropathy is insufficient production of a protein called otoferlin, which facilitates communication between the inner ear sensory cells and the auditory nerve. When this protein is lacking, the ear cannot communicate with the auditory nerve and the brain, resulting in profound hearing loss. Decibels lead investigational gene therapy program, DB-OTO, is designed to treat congenital, monogenic hearing loss caused by a deficiency in the otoferlin gene.

Amplify Program Eligibility

AmplifyTM is available to individuals who meet the following criteria:

AmplifyTM is a no-charge program that offers genetic testing for those who qualify. Although genetic testing can confirm a potential diagnosis, the absence of a genetic alteration does not preclude a diagnosis of genetic hearing loss. For more information about the program, please visit the Amplify program page.

About DB-OTO

DB-OTO is Decibels investigational gene therapy to restore hearing in children with congenital hearing loss due to a deficiency in the otoferlin gene. The program, developed in collaboration with Regeneron Pharmaceuticals, uses a proprietary, cell-selective promoter to precisely control gene expression in cochlear hair cells. DB-OTO is in preclinical studies, and Decibel expects to initiate clinical testing in 2022.

About Invitae

Invitae 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. Invitae's goal is to aggregate the world's genetic tests into a single service with higher quality, faster turnaround time, and lower prices. For more information, visit the company's website.

About Decibel Therapeutics

Decibel Therapeutics is a clinical-stage biotechnology company dedicated to discovering and developing transformative treatments to restore and improve hearing and balance, one of the largest areas of unmet need in medicine. Decibel has built a proprietary platform that integrates single-cell genomics and bioinformatic analyses, precision gene therapy technologies and expertise in inner ear biology. Decibel is leveraging its platform to advance gene therapies designed to selectively replace genes for the treatment of congenital, monogenic hearing loss and to regenerate inner ear hair cells for the treatment of acquired hearing and balance disorders. Decibels pipeline, including its lead investigational gene therapy program, DB-OTO, to treat congenital, monogenic hearing loss, is designed to deliver on our vision of a world in which the privileges of hearing and balance are available to all. For more information about Decibel Therapeutics, please visit http://www.decibeltx.com or follow @DecibelTx.

View source version on businesswire.com: https://www.businesswire.com/news/home/20210129005089/en/

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Decibel Therapeutics and Invitae Announce Launch of Amplify Genetic Testing Program - BioSpace

Today marked some wheeling and dealing in the life sciences industry as several companies licensed products or invested in other companies. Heres a look.

Eli Lillyand Asahi Kasei Pharma Eli Lilly and Company inked a license agreement with Tokyos Asahi Kasei Pharma Corporation. In it, Lilly picks up exclusive rights to AK1780 from Asahi. The drug is an oral P2X7 receptor antagonist that recently finished a Phase I dosing study. P2X7 receptors are associated with neuroinflammation that drives chronic pain conditions.

Under the terms of the deal, Lilly will handle future global development and regulatory activities. Lilly is paying Asahi Kasei Pharma $20 million up front and the Japanese company is eligible for up to $210 million in development and regulatory milestones. Asahi Kasei will retain the rights to promote the drug in Japan and China, including Hong Kong and Macau. If it makes it to market, Asahi Kesei will also be eligible for up to $180 million in sales milestones and tiered royalties from the mid-single to low-double digits.

Lilly is committed to developing novel medicines that may provide relief for patients suffering with various pain conditions, said Mark Mintun, vice president of pain and neurodegeneration research at Lilly. We are pleased to license this molecule from Asahi Kasei Pharma, and look forward to developing it further as a potential treatment for neuroinflammatory pain conditions.

Artiva Biotherapeutics and Merck San Diego-based Artiva Biotherapeutics announced an exclusive global collaboration and license agreement with Merck to develop novel chimeric antigen receptor (CAR)-NK cell therapies against solid tumor-associated antigens. They will leverage Artivas off-the-shelf allogeneic NK cell manufacturing platform and its proprietary CAR-NK technology. At first, the collaboration will include two CAR-NK programs with an option for a third. None of them are currently part of Artivas current or planned pipeline. Artiva will develop the programs through the first GMP manufacturing campaign and to preparation for the Investigational New Drug (IND) application, where Merck will take over clinical and commercial development.

Merck is paying Artiva $30 million upfront for the first two programs and another $15 million if Merck chooses to go ahead with the third. Artiva will be up for development and commercial milestones up to $612 million per program and royalties on global sales. Merck also is ponying up research funding for each program.

Our NK platform has been developed to be truly off-the-shelf and we believe it will be further validated by this exclusive collaboration with Merck, as we work together to bring cell therapies to all patients who may benefit, said Peter Flynn, chief operating officer of Artiva.

NeuBase Therapeutics and Vera Therapeutics Pittsburgh-based NeuBase Therapeutics announced a binding agreement to acquire infrastructure, programs and intellectual property for several peptide-nucleic acid (PNA) scaffolds from Vera Therapeutics, formerly called TruCode Gene Repair. Vera is based in South San Francisco. On January 19, Vera announced its launch with a $80 million Series C financing led by Abingworth LLP and joined by Sofinnova Investments, Longitude Capital, Fidelity Management & Research Company, Surveyor Capital, Octagon Capital, Kliner Perkins, GV and Alexandria Venture Investments. Veras lead clinical candidate is atacicept, a novel B cell and plasma cell inhibitor being developed for patients with IgA nephropathy (IgAN).

The technology acquired by NeuBase has shown the ability to resolve disease in genetic models of several disease indications. NeuBase is focused on genetic medicine.

With this acquisition, we enhance our PATrOL platform, furthering our unique ability to directly engage and correct malfunctioning genes with exquisite precision to address the root causes of a wide variety of human diseases, said Dietrich A. Stephan, chief executive officer of NeuBase. These assets extend and refine our PATrOL platforms capabilities and accelerates, through our Company, to bring the rapidly growing genetic medicines industry toward a single high-impact focal point. We are committed to advancing our pipeline and candidates to the clinic and to exploiting the full potential of PNA technology to continue creating value for our shareholders and importantly, for patients.

Bio-Techne Corporation and Changzhou Eminence Biotechnology Co Minneapolis-based Bio-Techne Corporation announced an initial minority strategic equity investment in Chinas Changzhou Eminence Biotechnology Co. Eminence plans to use the financing to expand its manufacturing capacity and increase the service capabilities of its China-based GMP media production facility. Eminence, based in Changzhou City, Jiangsu, China, launched in 2016 and initially focused on manufacturing and selling best-in-class media to life science companies, including Chinese Hamster Ovary (CHO) cells and other serum-free media products and services. The company is currently finishing and scaling its GMP production facility, which it plans to complete by the end of this year.

With our protein analysis instruments and expanding GMP protein capabilities, Bio-Techne continues to expand its offering of products and tools critical for bioprocessing, said Chuck Kumeth, president and chief executive officer of Bio-Techne. Investing in Eminence not only gives Bio-Techne a foothold in providing additional products and services to support the critical needs of the rapidly growing Chinese biopharmaceutical industry, but also fits extremely well with our existing high-growth product portfolio in China. We look forward to working with the Eminence team.

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4 New Life Sciences Licensing Deals and Investments to Watch - BioSpace

In recent years, the idea of the microbiome has gone from being an esoteric term used in scientific circles, to a mainstream concept employed in adverts to sell microbiome-boosting health drinks and supplements. The increase in public interest has been fed by a series of headline-grabbing research breakthroughs, and the fact that the microbiome has a key role to play in the development of precision medicine.The trillions of microbes contained in the human body are a key element of a personalized approach to treatment; the microbiome influences endocrinology, physiology, and even neurology, and has a crucial role in disease progression. The growing awareness of the various ways in which microbiota affects each of us individually in sickness and in health is also leading to an increase in research. An area in which this interest is growing particularly quickly is oncology.

Multiple publications implicate microbiota in the onset and progression of cancers, as well as toxicity and the response rate of cancer treatments. An analysis of 12 million full-text publications, 29 million abstracts and 521 thousand grant applications for semantic relations between cancers and microbiota is shown in figure 1. The data show a considerable increase in the number of articles linking cancers to microbiota for five cancer types with the highest number of reports overall.

Figure 1.Trend of reports linking cancers to microbiota 20082019. Credit: Graph generated using Elsevier Text Mining and Scopus.

With overall cancer rates set to increase worldwide, the current interest in the microbiome and its role in precision medicine is likely to continue because it offers new hope of treatments. Evidence suggests the importance of looking for predictors of therapeutic response beyond the tumor by focusing on host factors, such as microbiota and host genomics.1 Importantly, the microbiota is a modifiable factor, and potentially can become not just a predictive marker but also a potential target in order to improve outcomes for patients.

Progress is also being made in clinical trials looking at the microbiome and melanoma. Since 2018, four clinical trials that aim to study and modulate the gut microbiomes impact on response to immunotherapy of melanoma have been registered at clinicaltrials.gov. Dr Marc Hurlbert, Chief Science Officer for the Melanoma Research Alliance, commented on the findings: As noted in the report, there has been an explosion of knowledge about melanoma with an ever-increasing list of protein targets. Also noted, the role of the microbiome in melanoma and in response to immunotherapy is of increasing interest in the field.

To further develop targeted precision therapies, further research is now required. Firstly, to map genetic variants; secondly, to determine which variant is clinically significant; thirdly, to understand the impact of variant on gene function, and whether variation activates or inhibits the gene. This is particularly important for increased understanding of specific, precision medicine and to enhance therapeutic efficacy.

For non-hereditary (sporadic) melanoma, the analysis showed that there are 752 genes genetically linked to sporadic melanomas and its subtypes, and 449 genetic variants genetically linked to sporadic melanoma and its subtypes. Out of the 449 genetic variants, 395 are from 78 genes that are genetically linked to melanoma. The remaining missing 54 variants are not currently genetically linked in the platform to any known melanoma gene; this could therefore be a potential area for further research.

Understanding whether specific genetic variants exist and/or contribute to melanomas severity and prevalence in populations will help the research and development (R&D) industry to develop more effective and profitable therapeutics. These types of data will provide the R&D community with a greater depth of understanding and of the increased likelihood of hitting the target. Through our analysis we found an increased incidence of drugs targeting genetic mutations over the last decade, particularly targeting protein kinases and growth factor receptors.

It is an attractive future research avenue to recognize how a patients microorganisms genome, both symbiotic and pathogenic, can dramatically effect treatment plans and outcomes. Positively influencing the microbiome in patients needs further study that could lead to exciting opportunities for patients and for drug discovery. For the therapeutic pipeline it would be beneficial to understand these host-microbiota interactions and ways to positively tip the balance towards improving treatment outcomes.

One other interesting future consideration during drug development for all cancers is the influence of the microbiome on treatment-induced adverse events, and whether clinical and post-clinical adverse events are related to a patients microbial composition. It adds a level of complexity as to the efficacy of therapeutics that may not readily be considered, and potentially may be something to consider during future clinical trials.

Moreover, in the current COVID-19 era, in-person and patient interactions are reduced and many research labs are still unable to operate at full capacity. The ability to conduct research, take samples and study real patients is limited at present, so looking at detailed existing literature and data is a vital avenue to support R&D. It will keep R&D functions going and help them to direct efforts to the areas of greatest potential. 2021 will be a year of reduced R&D budgets globally this type of data insight will be vital to empowering future R&D.

Tom is the Life Sciences Group Manager of Project Management, Knowledge Manager, and Research Scientist. He has extensive experience as an academic researcher in neurodegeneration and Alzheimers disease. He is also skilled in biophysical chemistry, dementia disorders, and biochemistry. He is the author of many publications in the field of protein-membrane interactions, protein misfolding, and Alzheimers disease. At Elsevier he delivers and implements information solutions for customers.

Tom discusses the study and unmet needs in melanoma R&D in detail, here, alongside Marc Hurlbert, Ph.D. Chief Science Officer, Melanoma Research Alliance.

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Exploring the Relationship Between the Microbiome, Precision Medicine and Cancer - Technology Networks

Yuan-Yuan Li,* Sheng Zhang,* Hua Wang, Shun-Xiao Zhang, Ting Xu, Shu-Wen Chen, Yan Zhang, Yue Chen

Department of Endocrinology, Baoshan Branch, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201999, Peoples Republic of China

Correspondence: Yan Zhang; Yue ChenDepartment of Endocrinology, Baoshan Branch, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, No. 181 You-Yi Road, Shanghai, 201999, Peoples Republic of ChinaTel +86 13818856902; +86 13701994461Email yan_2999@hotmail.com; 13701994461@163.com

Background: Patients with diabetes have more calcification in atherosclerotic plaque and a higher occurrence of secondary cardiovascular events than patients without diabetes. The objective of this study was to identify crucial genes involved in the development of diabetic atherosclerotic plaque using a bioinformatics approach.Methods: Microarray dataset GSE118481 was downloaded from the Gene Expression Omnibus (GEO) database; the dataset included 6 patients with diabetic atherosclerotic plaque (DBT) and 6 nondiabetic patients with atherosclerotic plaque (Ctrl). Differentially expressed genes (DEG) between the DBT and Ctrl groups were identified and then subjected to functional enrichment analysis. Based on the enriched pathways of DEGs, diabetic atherosclerotic plaque-related pathways were screened using the comparative toxicogenomics database (CTD). We then constructed a proteinprotein interaction (PPI) network and transcription factor (TF)miRNAmRNA network.Results: A total of 243 DEGs were obtained in the DBT group compared with the Ctrl group, including 85 up-regulated and 158 down-regulated DEGs. Functional enrichment analysis showed that up-regulated DEGs were mainly enriched in isoprenoid metabolic process, DNA-binding TF activity, and response to virus. Additionally, DEGs participating in the toll-like receptor signaling pathway were closely related to diabetes, carotid stenosis, and insulin resistance. The TFmiRNAmRNA network showed that toll-like receptor 4 (TLR4), BCL2-like 11 (BCL2L11), and glutamate-cysteine ligase catalytic subunit (GCLC) were hub genes. Furthermore, TLR4 was regulated by TF signal transducer and activator of transcription 6 (STAT6); BCL2L11 was targeted by hsa-miR-24-3p; and GCLC was regulated by nuclear factor, erythroid 2 like 2 (NFE2L2).Conclusion: Identification of hub genes and pathways increased our understanding of the molecular mechanisms underlying the atherosclerotic plaque in patients with or without diabetes. These crucial genes (TLR4, BC2L11, and GCLC) might function as molecular biomarkers for diabetic atherosclerotic plaque.

Keywords: diabetes, atherosclerotic plaque, differentially expressed genes, bioinformatics analysis

Atherosclerosis is a chronic inflammation disease and the leading cause of morbidity and mortality globally.1 Atherosclerosis is a slowly progressive process, characterized by an accumulation of lipid in the arterial wall accompanied by multifocal structural alterations, leading to atheromatous plaque formation.2,3 Over time, the large necrotic lipid core is covered by a fibrous cap until, in advanced stages, the stability of the cap is destroyed, inducing plaque rupture and thrombosis, which can manifest as stroke or myocardial infarction. Cardiovascular disease is the leading cause of death in patients with diabetes.4 There is increasing evidence that diabetes induces hypercoagulability, which has a role in plaque rupture and increases the incidence and severity of clinical events.4

Previous researchers have reported the relationship between plaque characteristics and patients with and without diabetes. Burke et al indicated that total plaque in diabetic patients was significantly greater than that of nondiabetic individuals; in addition, the inflammatory response of diabetic plaques was stronger than that of nondiabetic plaque.5 An optical coherence tomography imaging study by Kato et al revealed that plaques in diabetic patients had a higher incidence of calcification and thrombus.6 Furthermore, van Haelst et al found that patients with diabetes had more calcification in atherosclerotic plaque and a higher occurrence of secondary cardiovascular events than patients without diabetes.7 Even though we can distinguish atherosclerotic plaque in diabetic and nondiabetic patients from morphologic fields, the effect of diabetes on gene expression in atherosclerotic plaque is not fully understood.

Macrophage accumulation plays a vital role in both plaque progression and stability, which can promote inflammation and aggravate disease.8,9 Thus, we selected a gene expression dataset (GSE118481) containing diabetic plaque macrophage (DBT) and nondiabetic plaque macrophage (Ctrl) for analysis. Differentially expressed genes (DEGs) between the DBT and Ctrl groups were identified, functional enrichment analysis of the DEGs was performed, and disease-related pathways were screened. We then constructed a proteinprotein interaction (PPI) network and sub-network. Subsequently, microRNA (miRNA) and transcription factors (TFs) of DEGs were predicted and an integrated TFmiRNAmRNA network was constructed. The analysis process of this study is shown in Supplementary Figure 1. We aimed to further understand the molecular mechanism by which diabetes promotes the formation of atherosclerotic plaque and to determine potential gene targets for personalized diagnosis and treatment strategies of diabetic atherosclerotic plaque.

The gene expression profile GSE118481 based on the GPL10558 Illumina HumanHT-12 V4.0 expression BeadChip platform was downloaded from the Gene Expression Omnibus (GEO) database (website: http://www.ncbi.nlm.nih.gov/geo/).10 This microarray data set included 16 nondiabetic samples (6 asymptomatic and 10 symptomatic) and 8 diabetic plaque samples (6 asymptomatic and 2 symptomatic). In order to study the effect of diabetes on atherosclerotic plaque, we selected asymptomatic samples for subsequent analysis. Therefore, 12 samples (6 DBT and 6 Ctrl) were included, and the clinical characteristics of these patients are listed in Supplementary Table 1. There were no significant differences in age (P = 0.24) and sex (P > 0.05) between the two groups.

The series matrix file for GSE118481 dataset was obtained from the GEO database,10 and the expression data of 6 DBT and 6 Ctrl macrophage samples were extracted for further analysis. Microarray expression profiling was standardized by Bioconductor bead array package,11 and the distribution of expression in each sample was visualized by boxplots. The probe ID was converted to a gene symbol using the annotation file, and probes that did not mapped to gene symbols were removed. If multiple probes matched the same gene, the mean value of probes was calculated. Empirical Bayes moderated t-test in the limma package (version 3.40.6)12 was used to identify DEGs between DBT and Ctrl samples. DEGs with P < 0.05 and |log fold change (FC)| >0.585 were considered statistically significant. The ggplot2 and heatmap of R (http://www.R-project.org/) were utilized to visualize the DEGs.

Using Pearson correlation coefficients (r) in the stats of R package (version 3.6.1; http://www.R-project.org/), the co-expression of DEGs in DBT and Ctrl samples was, respectively, analyzed. Pairs with r > 0.95 and P < 0.05 were selected for further study. Cytoscape was applied to construct a co-expression network of Ctrl and DBT groups, and then the topological properties of the two networks were analyzed by using CytoNCA in Cytoscape.13 Furthermore, t-tests were used to calculate the difference between Ctrl and DBT networks. The sub-networks of DBT group were structured using the Cytoscape MCODE plugin,14 and networks with a score >3 were selected.

To understand the major biological functions of DEGs, we analyzed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of up- and down-regulated DEGs using the clusterProfiler package. Significant enrichment was defined by P < 0.05 and count >2.

Diabetes, carotid stenosis, and insulin resistance have effects on the development of diabetic atherosclerotic plaque. Therefore, to further identify diabetic plaque-related pathways, we screened pathways relevant to these diseases from the comparative toxicogenomics database (CTD), and these pathways were integrated with the KEGG pathways in the previous step.

To determine the relationships among DEGs, we mapped the DEGs to the Search Tool for the Retrieval of Interacting Genes (STRING, version 11.0, http://www.string-db.org/) database, and only interactions with a combined score >0.7 were selected. Then, Cytoscape software was used to establish the PPI network, and hub nodes in the network were identified by CytoNCA. The PPI network was further analyzed by MCODE to explore functional modules, and score >5 was selected as the threshold.

To further understand the regulatory mechanism of DEGs, miRNAs of target genes were predicted using four available databases: miRWalk3.0,15 TargetScan,16 MiRDB,17 and MirTarBase.18 Putative miRNAs with score >0.95 and supported by at least two databases were selected; additionally, TFtarget interactions were predicted by Transcriptional Regulatory Relationships Unraveled by Sentence-based Text mining (TRRUST) (https://www.grnpedia.org/trrust/).19 Subsequently, miRNAtarget pairs and TFtarget pairs were integrated to construct the TFmiRNAmRNA regulatory network.

The raw data were processed and the boxplots showed good normalized properties (Figure 1A). A total of 33,984 probes were obtained after annotation. A total of 243 DEGs were identified between the DBT and Ctrl groups, including 85 up-regulated and 158 down-regulated DEGs. The heat map and volcano plot of DEGs are shown in Figure 1B and C.

Figure 1 Gene expression profile data analysis. (A) Boxplot of gene expression data after normalization. (B) Heat map of DEGs between Ctrl and DBT groups; green indicates Ctrl group and red indicates DBT group. (C) Volcano plot of DEGs between Ctrl and DBT groups.

Co-expression network analysis showed that 144 pairs and 162 DEGs were identified in the Ctrl group (Figure 2A), and 191 relationships and 170 DEGs were screened in the DBT group (Figure 2B). The topological properties of the Ctrl and DBT networks indicated that betweenness, closeness, and degree values were significantly higher in the DBT group than in the Ctrl group (Figure 2C), suggesting that co-expression of DEGs was more abundant in the DBT group than in the Ctrl group. The sub-network (score = 3.333) of the DBT group was constructed and included serine/threonine kinase 32B (STK32B), tripartite motif containing 22 (TRIM22), ninjurin 2 (NINJ2), and transmembrane protein 114 (TME114) (Figure 2D).

Figure 2 Disease-related co-expression network. (A) Co-expression network of Ctrl group. (B) Co-expression network of DBT group. (C) Topology properties of Ctrl and DBT group co-expression network. (D) Sub-network of DBT group. Red nodes indicate up-regulated DEGs, blue nodes indicate down-regulated DEGs, red lines represent positive correlation, and blue lines represent negative correlation. *Indicates the average of the data in each group.

Functional enrichment analysis of up-regulated and down-regulated DEGs was performed using the clusterProfiler tool. The top 10 significantly enriched GO terms and KEGG pathways are shown in Figure 3A and B. The up-regulated DEGs were significantly enriched in GO terms related to isoprenoid metabolic process, response to estradiol, and retinal metabolic process, and the down-regulated DEGs were markedly associated with regulation of DNA-binding TF activity, alpha-amino metabolic process, and response to virus (Figure 3A). For the KEGG pathway analysis, up-regulated DEGs were primarily involved in adipocytokine signaling pathway, cosphingolipid biosynthesis-lacto and neolacto series, and non-alcoholic fatty liver disease; in addition, down-regulated DEGs were mainly involved in folate biosynthesis, cysteine and methionine metabolism, and Chagas disease (American trypanosomiasis) pathways (Figure 3B).

Figure 3 Functional enrichment analysis of DEGs. (A) GO analysis of the DEGs. (B) KEGG pathway analysis of the DEGs. The y-axis represents the GO terms or KEGG pathways, and the x-axis represents up-regulated and down-regulated DEGs. The size of bubbles represents the number of assigned genes, and the color of bubbles represents the adjusted P-value. The greater the number of DEGs associated with the term or pathway, the larger the bubble.

A total of 13 pathways were closely related to diabetes mellitus, one pathway was associated with carotid stenosis, and 10 pathways were associated with insulin resistance (Table 1). All three of these diseases were relevant to the toll-like receptor signaling pathway. Genes such as toll-like receptor 8 (TLR8), toll-like receptor 4 (TLR4), mitogen-activated protein kinase 4 (MAP2K4), and interferon regulatory factor 5 (IRF5) were involved in this pathway. In addition, 10 pathways were related to diabetes mellitus and insulin resistance, including acute myeloid leukemia, influenza A, non-alcoholic fatty liver disease (NAFLD), and adipocytokine signaling.

Table 1 Disease-Related Pathways Analysis

The 225 proteins encoded by DEGs were searched in the STRING database and then used to construct the PPI network, which included 76 nodes and 114 pairs of edges (Figure 4A). Among these, several nodes with a higher degree [2-5-oligoadenylate synthetase 2 (OAS2, degree = 15), IRF5 (degree = 11), guanylate binding protein 1 (GBP1, degree = 11), and interferon-induced protein with tetratricopeptide repeats 3 (IFIT3, degree = 11)] could be considered hub proteins. Additionally, a module with score >5 was identified using the MCODE plugin. This sub-network was composed of 12 nodes and 43 pairs (Figure 4B). OAS2 (degree = 5), radical s-adenosyl methionine domain containing 2 (RSAD2, degree = 6), and eukaryotic translation initiation factor 2 alpha kinase 2 (EIF2AK2, degree = 5) were involved in diabetes and insulin resistance-related pathways.

Figure 4 PPI network. (A) PPI network composed of 76 nodes and 114 edges. (B) Sub-network consisted of 12 nodes and 43 pairs. Triangle indicates up-regulated DEG, V-shape indicates down-regulated DEGs. Blue represent genes not involved in diseases-related pathways, yellow represent genes involved in diabetes-related pathways, green indicate genes enriched in diabetes and insulin resistance pathways, and red indicates genes participated in diabetes, insulin resistance, and plaque pathways.

After screening, 102 miRNAmRNA pairs and 114 TF-mRNA pairs were predicted, and then these pairs were integrated to structure a TFmiRNAmRNA regulatory network. A total of 154 interactions were identified, involving 57 genes, 30 miRNA, and 75 TFs (Figure 5). In this regulatory network, we noted glutamate-cysteine ligase catalytic subunit (GCLC), BCL2 like 11 (BCL2L11), and TLR4 had higher degrees. GCLC was targeted by the TF nuclear factor, erythroid 2 like 2 (NFE2L2); BCL2L11 was targeted by hsa-miR-24-3p, and regulated by TF forkhead box O3 (FOXO3), and TLR4 was related to the process of three diseases and regulated by TF signal transducer and activator of transcription 6 (STAT6).

Figure 5 The TFmiRNAmRNA regulatory network. Red nodes represent up-regulated DEGs, blue nodes represent down-regulated DEGs, green triangles represent miRNAs, green diamonds represent TF, and blue and red diamonds represent both TF and DEGs. Red lines indicate activation relationships and blue lines indicate inhibitory relationships.

Abbreviations: TF, transcription factor; miRNA, microRNA; mRNA, messenger RNA; DEG, differentially expressed gene.

Diabetes is known to be associated with atherosclerotic plaque; however, the underlying molecular mechanism of the effect of diabetes on atherosclerotic plaque has not been fully elucidated. We analyzed gene expression patterns involved in diabetic atherosclerotic plaque using the dataset GSE118481. The results revealed that the toll-like receptor signaling pathway was associated with the pathogenesis of diabetic atherosclerotic plaque. Additionally, TLR4, BCL2L11, and GCLC were potential biomarkers for atherosclerotic plaque in patients with diabetes.

The formation and progression of atherosclerotic plaque is related to the accumulation of monocyte-derived macrophage in the arterial wall. Compared with patients without diabetes, the plaques in the coronary arteries of patients with diabetes gene generally exhibit larger necrotic cores and significantly greater inflammation, mainly composed of macrophages and T lymphocytes.20 Based on analysis of disease-related pathways, we observed that the toll-like receptor signaling pathway was significantly associated with diabetes mellitus, carotid stenosis, and insulin resistance; additionally, hub gene TLR4 was involved in this pathway. Madhur et al21 indicated that inflammation response could reduce the stability of atherosclerotic plaques in animal models. It is reported that the TLR signaling pathway is associated with systemic inflammation and immune response, and participates in angiogenesis, survival, and repair.22,23 Meanwhile, TLR4, as a member of the TLR family, is believed to activate nuclear factor-B in response to short-chain fatty acids, triggering further activation of the immune system.24 Thus, TLR4 induced inflammation plays an important role in atherosclerotic plaque stability. Xu et al demonstrated that TLR4 was preferentially expressed by macrophages in human lipid-rich atherosclerotic lesions, where it might play a role to enhance and maintain the innate immunity and inflammation. In addition, the up-regulation of TLR4 in macrophages by oxidized low-density lipoprotein (LDL) suggested that TLR4 might provide a potential pathophysiological link between lipids as well as inflammation and atherosclerosis.25 In this analysis, we also found the relationship between TLR4 and diabetes. Devaraj et al demonstrated that expression of TLR4 was significantly increased in patients with type 1 diabetes, suggesting that TLR4 contributes to the pro-inflammatory state in diabetes.26 Moreover, knockout of TLR4 might alleviate inflammation in diabetic rats27 and TLR4 antagonist could attenuate atherogenesis in mice with diabetes.28 The antidiabetic drug class thiazolidinediones (TZDs) have been reported to reduce the risk of atherosclerosis in patients with type 2 diabetes, which might have an anti-atherosclerotic effect by inhibiting the TLR4 signaling pathway.29 These findings emphasized the importance of TLR4 in plaque formation of patients with diabetes. In the present study, we found that TLR4 was regulated by the TF STAT6. STAT6 has a major role in the immune system30 and is associated with macrophage polarization, which is critically involved in atherosclerosis progression and regression.31 Based on our results, we speculated that TLR4 and STAT6 might participate in the pathogenesis of diabetic atherosclerotic plaque via the TLR signaling pathway.

In the regulatory network, BCL2L11 had higher degree and was considered a hub gene. BCL2L11 encodes BCL-2 protein family, and its members participate in various cellular activities as anti- or proapoptotic regulators.32 A previous study revealed that BCL2L11 was connected to apoptosis of podocytes in diabetes.33 However, there are few reports about the association between BCL2L11 and carotid plaque. Our analysis showed that BCL2L11 was targeted by hsa-miR-24-3p. Erener et al observed that miR-24-3p was an effective biomarker to predict and diagnose diabetes.34 Moreover, miR-24-3p was found to limit macrophage vascular inflammation and slow the progression of atherosclerotic plaque.35 Taken together, hsa-miR-24-3p might affect the progression of diabetic atherosclerotic plaque by directly targeting BCL2L11. However, the specific regulatory mechanism of BCL2L11 in diabetic atherosclerotic plaque needs further elaboration.

We also found that GCLC was closely related to diabetic atherosclerotic plaque. GCLC is a rate-limiting enzyme of glutathione synthesis, and it is involved in susceptibility to myocardial infarction.36 Callegari et al found that the gain and loss of the ability to synthesize glutathione especially in macrophages had reciprocal effects on the initiation and progression of atherosclerosis at multiple sites in apoE-/- mice.37 Jain et al reported that the plasma level of GCLC was lower in diabetic patients than in healthy controls.38 Moreover, the GCLC polymorphism was associated with cellular redox imbalances and modulate the risk for diabetic nephropathy.39 In the TFmiRNAmRNA network, GCLC was regulated by NFE2L2 (also known as NRF2), which is considered to be a master regulator of the antioxidant response.40 It regulates the expression of several genes including Phase II metabolic and antioxidant enzymes, and therefore plays an important role in preventing oxidative stress-mediated diabetes and related complications.41 In addition, overexpression of Nrf2 could protect pancreatic cells from oxidative damage in diabetes.42 Furthermore, a study by Harada et al revealed that activation of Nrf2 was observed in advanced atherosclerotic plaques, suggesting that Nrf2 might influence the inflammatory reactions in the plaques.43 Thus, we speculated that GCLC targeted by NFE2L2 might participate in the pathogenesis of diabetic atherosclerotic plaque.

Some limitations should be noted in the current study. First, the sample size of this study was small; further investigations based on a larger sample should be performed. Second, hub genes were identified using bioinformatics analysis; thus, experimental studies are needed to validate our results. Despite these limitations, this study provided some new insights into the pathogenesis and treatment of diabetic atherosclerotic plaques. Further large-scale studies are needed to corroborate these findings and investigate the potential underlying mechanisms involved. Meanwhile, clinical trials with more detailed investigation are also warranted before genes such as TLR4, BCL2L11, GCLC can be used in clinical setting.

In summary, we have conducted a comprehensive bioinformatics analysis of DEGs between diabetic and nondiabetic atherosclerotic plaque. Several genes have been identified with different expression patterns in diabetic and non-diabetic atherosclerotic plaque, such as TLR4, BCL2L11, GCLC, STAT6, and NFE2L2, as well as hsa-miR-24-3p. Meanwhile, pathway analysis showed that these genes were involved in the toll-like receptor signaling pathway. These findings provided better understanding of the underlying molecular mechanisms of diabetic atherosclerotic plaque. However, further research of these candidate genes was needed to confirm their effects in diabetic atherosclerotic plaque.

We thank Louise Adam, ELS(D), from Liwen Bianji, Edanz Editing China (www.liwenbianji.cn/ac) for editing the English text of a draft of this manuscript.

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work; Yan Zhang and Yue Chen are the co-corresponding authors of this study.

This study was supported by the National Natural Science Foundation of China (82004117), Baoshan medical speciality project (BSZK-2018-A02), and the Cultivation Fund of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine for NSFC (Grant Number: GZRPYJJ-201803).

The authors declare that they have no conflicts of interest for this work.

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[Full text] Identification of Crucial Genes and Pathways Associated with Atheroscl | PGPM - Dove Medical Press

Gene therapy veteran Ronald Crystal, M.D., has seen it all.

Ive been in the gene therapy field since the beginning, 1987 or so, so Ive seen the wild period, the dark days, and now were back to the wild period, he said.

And one thing he'srealized after being in the field for so long? "Inthe academic world, we are very, very good at coming up with ideas, developing preclinical evidence and moving to the IND stages. But clinical studies much better belong in a company.

Virtual Clinical Trials Summit: The Premier Educational Event Focused on Decentralized Clinical Trials

In this virtual environment, we will look at current and future trends for ongoing virtual trials, diving into the many ways companies can improve patient engagement and trial behavior to enhance retention with a focus on emerging technology and harmonized data access across the clinical trial system.

So,he started one: Lexeo Therapeutics. Founded with National Institutes of Health small business grants in early 2018, the company is coming out of stealth with $85 million in series A cash;18 preclinical and clinical programs primarily developed at Weill Cornell Medicine, where Crystal is a professor and chairman of the department of genetic medicine;and a star-studded team to move it all forward.

RELATED: Taysha Gene Therapies hits the ground running with $30M, 15 programs

Our view is the gene therapy field today is very much focused on rare, monogenic diseases, said Lexeo CEO Nolan Townsend, who previously led rare disease work at Pfizer. The vision we have for gene therapy is it will eventually move to larger diseases, and we have the pipeline to support that vision.

Two of Lexeos lead programs are in rare diseases: Friedreichs ataxia and Batten disease. And its18 programs span rare and more prevalent monogenic diseasesi.e., those caused by a defect in a single geneas well as acquired diseases, which just means diseases that strike during a persons lifetime rather than those that affectthem from birth.

The funding, drawn from the likes of Longitude Capital, Omega Funds, the Alzheimers Drug Discovery Foundation and Alexandria Venture Investments, will push Lexeos three lead programs through the clinic. Its Friedreichs ataxia program is slated to enter phase 1 this year, and its Batten disease treatment has finished a phase 1/2 study and is set for a pivotal trial in 2022. Lexeo is developing its third program for the treatment of Alzheimers disease in people with the APOE4 gene, a variant known to increase the risk of developing the disease. It is in phase 1.

Besides bankrolling its clinical trials, Lexeo is using a meaningful portion of the funding to invest in manufacturing, a major bottleneck in gene therapy. And thats not allthe company is headquartered in New York City and hopes to play a role in building the citys life sciences network.

RELATED: Avrobio tracks improvements in first patient treated with Gaucher gene therapy

Joining Crystal and Townsend is chairmanSteven Altschuler, M.D., the managing director at Ziff Capital Investments who used to chair the board of gene therapy biotech Spark Therapeutics. The company has also recruited Jay Barth, M.D., as chief medical officer. Barth previously held the same role at Amicus Therapeutics, where he oversaw clinical development in rare disease and gene therapy, including the approval of Fabry disease med Galafold.

Lexeo isnt the only new gene therapy player on the block. A group of former AveXis executives and investors unveiled their second act in April last year: Taysha Gene Therapies, which launched with $30 million and 15 programs licensed from UT Southwestern Medical Center. The next month, Kriya Therapeutics debuted with $80.5 million and a mission to develop gene therapies for more complex and more common diseases.

Continued here:
Lexeo Therapeutics emerges with $85M, 18 gene therapy programs and a star-studded team - FierceBiotech

DBMR has added a new report titled Global Precision Medicine Market with analysis provides the insights which bring marketplace clearly into the focus and thus help organizations make better decisions. This Global Precision Medicine Market research report understands the current and future of the market in both developed and emerging markets. The report assists in realigning the business strategies by highlighting the business priorities. It throws light on the segment expected to dominate the industry and market. It forecast the regions expected to witness the fastest growth. This report is a collection of pragmatic information, quantitative and qualitative estimation by industry experts, the contribution from industry across the value chain. Furthermore, the report also provides the qualitative results of diverse market factors on its geographies and Segments.

Global Precision Medicine Market to grow with a substantial CAGR in the forecast period of 2019-2026. Growing prevalence of cancer worldwide and accelerating demand of novel therapies to prevent of cancer related disorders are the key factors for lucrative growth of market

Global Precision Medicine Market By Application (Diagnostics, Therapeutics and Others), Technologies (Pharmacogenomics, Point-of-Care Testing, Stem Cell Therapy, Pharmacoproteomics and Others), Indication (Oncology, Central Nervous System (CNS) Disorders, Immunology Disorders, Respiratory Disorders, Others), Drugs (Alectinib, Osimertinib, Mepolizumab,Aripiprazole lauroxil and Others), Route of Administration (Oral,Injectable), End- Users (Hospitals, Homecare, Specialty Clinics, Others), Geography (North America, South America, Europe, Asia-Pacific, Middle East and Africa) Industry Trends and Forecast to 2026

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Competitive Analysis:

The precision medicine market is highly fragmented and is based on new product launches and clinical results of products. Hence the major players have used various strategies such as new product launches, clinical trials, market initiatives, high expense on research and development, agreements, joint ventures, partnerships, acquisitions, and others to increase their footprints in this market. The report includes market shares of mass spectrometry market for global, Europe, North America, Asia Pacific and South America.

Market Definition:

Precision medicines is also known as personalized medicines is an innovative approach to the patient care for disease treatment, diagnosis and prevention base on the persons individual genes. It allows doctors or physicians to select treatment option based on the patients genetic understanding of their disease.

According to the data published in PerMedCoalition, it was estimated that the USFDA has approved 25 novels personalized medicines in the year of 2018. These growing approvals annually by the regulatory authorities and rise in oncology and CNS disorders worldwide are the key factors for market growth.

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Market Drivers

Market Restraints

Key Developments in the Market:

Competitive Analysis:

Global precision medicine market is highly fragmented and the major players have used various strategies such as new product launches, expansions, agreements, joint ventures, partnerships, acquisitions, and others to increase their footprints in this market. The report includes market shares of global precision medicine market for Global, Europe, North America, Asia-Pacific, South America and Middle East & Africa.

Key Market Players:

Few of the major competitors currently working in the global precision medicine market are Neon Therapeutics, Moderna, Inc, Merck & Co., Inc, Bayer AG, PERSONALIS INC, GENOCEA BIOSCIENCES, INC., F. Hoffmann-La Roche Ltd, CureVac AG, CELLDEX THERAPEUTICS, BIONTECH SE, Advaxis, Inc, GlaxoSmithKline plc, Bioven International Sdn Bhd, Agenus Inc., Immatics Biotechnologies GmbH, Immunovative Therapies, Bristol-Myers Squibb Company, Gritstone Oncology, NantKwest, Inc among others.

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Market Segmentation:

By technology:- big data analytics, bioinformatics, gene sequencing, drug discovery, companion diagnostics, and others.

By application:- oncology, hematology, infectious diseases, cardiology, neurology, endocrinology, pulmonary diseases, ophthalmology, metabolic diseases, pharmagenomics, and others.

On the basis of end-users:- pharmaceuticals, biotechnology, diagnostic companies, laboratories, and healthcare it specialist.

On the basis of geography:- North America & South America, Europe, Asia-Pacific, and Middle East & Africa. U.S., Canada, Germany, France, U.K., Netherlands, Switzerland, Turkey, Russia, China, India, South Korea, Japan, Australia, Singapore, Saudi Arabia, South Africa, and Brazil among others.

In 2017, North America is expected to dominate the market.

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Global Precision Medicine Market 2020 Overview By Size, Share, Trends, Growth Factors and Leading Players With Detailed Analysis of Industry Structure...