Category Archives: Genetic medicine

Russian Geographical Society

When you hold a job like Defense Minister of Russia, you presumably have to be bold and think outside the box to protect your country from enemy advances. And with his latest strategic ideacloning an entire army of ancient warriorsSergei Shoigu is certainly taking a big swing.

In an online session of the Russian Geographical Society last month, Shoigu, a close ally of Russian President Vladimir Putin, suggested using the DNA of 3,000-year-old Scythian warriors to potentially bring them back to life. Yes, really.

First, some background: The Scythian people, who originally came from modern-day Iran, were nomads who traveled around Eurasia between the 9th and 2nd centuries B.C., building a powerful empire that endured for several centuries before finally being phased out by competitors. Two decades ago, archaeologists uncovered the well-preserved remains of the soldiers in a kurgan, or burial mound, in the Tuva region of Siberia.

Because of Tuvas position in southern Siberia, much of it is permafrost, meaning a form of soil or turf that always remains frozen. Its here where the Scythian warrior saga grows complex, because the frozen soil preserves biological matter better than other kinds of ground. Russian defense minister Sergei Shoigu knows this better than anyone, because hes from Tuva.

Of course, we would like very much to find the organic matter and I believe you understand what would follow that, Shoigu told the Russian Geographical Society. It would be possible to make something of it, if not Dolly the Sheep. In general, it will be very interesting.

Shoigu subtly suggested going through some kind of human cloning process. But is that even possible?

To date, no one has cloned a human being. But scientists have successfully executed the therapeutic cloning of individual kinds of cells and other specific gene-editing work, and of course, there are high-profile examples of cloning pretty complex animals. Earlier this year, for example, scientists cloned an endangered U.S. species for the first time: a black-footed ferret whose donor has been dead for more than 30 years.

So, why are humans still off the menu?

Blame a technical problem with the most common form of cloning, which is called nuclear transfer. In this process, a somatic cell (like a skin or organ cell, with a specific established purpose in the body) has its nucleus carefully lifted out, and this nucleus is deposited in an oocyte, or egg cell, with its nucleus carefully removed. Its like a blank template waiting to have a new nucleus swapped in.

gremlinGetty Images

From a technical perspective, cloning humans and other primates is more difficult than in other mammals, the National Institutes of Healths (NIH) National Human Genome Research Institute says on its website:

You might remember spindle proteins from your mitosis diagrams back in high school biology. And while theres a relatively easy way around this problem, its almost moot when cloning humans is considered extremely taboo in most of the world. In some places, its also explicitly illegal.

We would like very much to find the organic matter and I believe you understand what would follow that.

Curiously, the U.S. hasnt banned the gene editing of embryos. But the NIH doesnt fund research on the practice, and places like in-vitro clinics arent allowed to do any non-U.S. Food and Drug Administration-approved manipulation of embryos under any circumstances.

That example starts to illustrate why the problem is so complexbecause a lot of cutting-edge genetic medicine is walking right up to the line without crossing it. Making laws that address full human embryo cloning, then, requires a jigsaw puzzle of careful language that doesnt rule out these kinds of therapeutic cloning.

HandoutGetty Images

But lets say Russia ignores all legality in favor of Shoigus big plans. In that case, scientists would have to develop a way to lift out the human nucleus without damaging the cell beyond repair.

Scientists have cloned certain monkeys, so primates are at least hypothetically still in the mix, despite the spindle proteins. But the success rate even for non-primate clones is already very lowit took Dolly the sheeps research team 277 attempts to get a viable embryo.

And what if all of that went perfectly? Well, the Scythians were powerful warriors and gifted horsemen, but scientistsor the Kremlinmust carefully monitor a cloned baby version of a deceased adult warrior for illnesses and other prosaic childhood problems. Who will raise these children? Who will be legally responsible for their wellbeing?

Shoigu may envision a future race of extremely capable fighters, but ... thats at least 20 years away, with an added coin flip on nature versus nurture. After all, the Scythian warriors didnt have plumbing, let alone smartphones. This is a whole new world.

This content is created and maintained by a third party, and imported onto this page to help users provide their email addresses. You may be able to find more information about this and similar content at piano.io

More:
Russia Is Going to Try to Clone an Army of 3,000-Year-Old Scythian Warriors - Popular Mechanics

VANCOUVER, BC, Feb. 2, 2021 /PRNewswire/ -Precision NanoSystems, Inc. (PNI), a global leader in technologies and solutions for development of genetic medicines, announced today that it has received a contribution of CAD $25.1 million through the Strategic Innovation Fund (SIF). This contribution will support a CAD $50.2-million project to establish a biomanufacturing centre in Vancouver dedicated to the production of ribonucleic acid (RNA) lipid nanoparticle vaccines and genetic medicines. The centre will support the Government of Canada's national biomanufacturing strategy to expand production capacity of critical medicines for the prevention and treatment of diseases such as COVID-19.

"Our government is bringing back the vaccine manufacturing capacity that Canadians expect and need. These investments will help to ensure that Canada has modern, flexible vaccine manufacturing capabilities now and in the future. With the investments announced today, our government is helping Canadian companies advance made-in-Canada vaccines and therapies, while securing domestic manufacturing options for international vaccine candidates. This is all part of our government's commitment to protect the health and safety of all Canadians today, and in the future", said the Honourable Franois-Philippe Champagne, Minister of Innovation, Science and Industry.

PNI supports the development of genetic medicines by providing products and services to its clients worldwide who are creating new treatments for infectious diseases, rare diseases, cancer and other areas of unmet need. This project will help PNI establish a Biomanufacturing Centre that will expand Canada's epidemic and pandemic preparedness capacity and will enable PNI to expand its development and manufacturing services to support the clinical development and supply of new medicines.

"PNI's centre of manufacturing excellence of nanomedicine will be a state-of-the-art facility for the development and manufacture of genetic therapeutics and vaccines," James Taylor, CEO, Precision NanoSystems stated. "The centre will continue Canada's leadership in the creation of innovative solutions for the development and production of new medicines for the benefit of patients in Canada and beyond. This support from the Government of Canada helps PNI to further achieve our mission of accelerating the creation of transformative medicines that significantly impact human well-being."

About Precision NanoSystems Inc. (PNI)

PNI is a global leader in ushering in the next wave of genetic medicines in infectious diseases, cancer and rare diseases. We work with the world's leading drug developers to understand disease and create the therapeutics and vaccines that will define the future of medicine.PNI offers proprietary technology platforms and comprehensive expertise to enable researchers to translate disease biology insights into non-viral genetic medicines.

View original content to download multimedia:http://www.prnewswire.com/news-releases/precision-nanosystems-receives-contribution-from-the-government-of-canada-to-build-rna-medicine-biomanufacturing-centre-301220444.html

SOURCE Precision Nanosystems

View original post here:
Precision NanoSystems Receives Contribution from the Government of Canada to Build RNA Medicine Biomanufacturing Centre - BioSpace

Vancouver, British Columbia, Feb. 04, 2021 (GLOBE NEWSWIRE) -- The Global Regenerative Medicine Market is predicted to attain a market valuation of USD 6.49 billion by 2027, growing at a CAGR of 9.3% throughout the estimated period, according to a recent analysis by Emergen Research. Targeted therapy of specific disease indication and chronic illnesses are anticipated to alter the dynamics of the healthcare field. The escalating prevalence of chronic health conditions and increasing patient pool of geriatric populace coupled with neurodegenerative disorders, cancers, orthopedic, and other age-related conditions are further bolstering the industrys expansion.

The numerous applications and subsequent advancements in tissue engineering, gene therapy, nanotechnology, and stem cells research are foreseen to boost the scope of regenerative medicine. 3D printing is playing a pivotal role in stem cells research as it allows for the easy restoration of structural and functional properties.

North America is predicted to occupy a significant share of the market in the projected timeframe and the growth can be attributed to the increasing number of academic institutions and universities extensively exploring regenerative medicine approaches based on stem cells.

Claim Your FREE Sample Copy with Table of content@ https://www.emergenresearch.com/request-sample-form/9

Key Highlights from the Report:

Claim Your FREE Sample Copy with Table of content@ https://www.emergenresearch.com/request-sample-form/9

For the purpose of this report, Emergen Research has segregated the Global Regenerative Medicine Market on the basis of product, therapeutic category, application, and region:

Product Outlook (Volume, Million Tons; Revenue, USD Billion; 2017-2027)

Therapeutic Category Outlook (Volume, Million Tons; Revenue, USD Billion; 2017-2027)

Application Outlook (Volume, Million Tons; Revenue, USD Billion; 2017-2027)

Click to access the Report Study, Read key highlights of the Report and Look at Projected Trends: https://www.emergenresearch.com/industry-report/regenerative-medicine-market

Regional Outlook (Volume, Million Tons; Revenue, USD Billion; 2017-2027)

Take a Look at our Related Reports:

Topical Drug Delivery Market By Product Form (Semi-Solid, Solid Formulations, Transdermal Products, and Liquid Formulations), By Route (Dermal, Ophthalmic, Nasal, Others), By End-Use (Hospitals, Home Healthcare, Clinics, Diagnostic Centers, Burn Center), and By Regions

Medical Smart Textiles Market By Technology (Textile Sensors, Wearable Technology), By Application (Surgery, Bio-Monitoring, Therapy, and Wellness), By End-use (Hospitals and Clinics, Medical Academic and Research Center), and By Region

Operating Room Management Solutions Market By Solution Type (Data management and communication solutions, Operating room supply management solutions, Anesthesia information management solutions, Operating room scheduling solutions, Performance management solutions), By Mode of Deployment (Ob-premises, Cloud-based), By End-Use (Hospitals, Ambulatory surgical centers), and By Region

Patient Registry Software Market By Delivery, By Database, By Registry Type, By Function, By Software Type (Integrated, Standalone), By End-use (Government & Third-Party Administrators, Pharmaceutical Companies, Hospitals, Research Centers, Others), and By Region, Forecast to 2027

Ambulatory EHR Market By Deployment (Cloud-based, On-premises), By Practice Size (Solo Practices, Large Practices, Small-medium-sized Practices), By Application, By End-use (Independent Centers, Hospital-owned Ambulatory Centers, Others), and By Region, Forecasts to 2027

About Emergen Research

Emergen Research is a market research and consulting company that provides syndicated research reports, customized research reports, and consulting services. Our solutions purely focus on your purpose to locate, target, and analyze consumer behavior shifts across demographics, across industries, and help clients make smarter business decisions. We offer market intelligence studies ensuring relevant and fact-based research across multiple industries, including Healthcare, Touch Points, Chemicals, Types, and Energy. We consistently update our research offerings to ensure our clients are aware of the latest trends existent in the market. Emergen Research has a strong base of experienced analysts from varied areas of expertise. Our industry experience and ability to develop a concrete solution to any research problems provides our clients with the ability to secure an edge over their respective competitors.

Contact Us:

Eric Lee

Corporate Sales Specialist

Emergen Research | Web: http://www.emergenresearch.com

Direct Line: +1 (604) 757-9756

E-mail: sales@emergenresearch.com

Facebook | LinkedIn | Twitter | Blogs

Read Full Press Release: https://www.emergenresearch.com/press-release/global-regenerative-medicine-market

Continue reading here:
Regenerative Medicine Market to be Valued at USD 6.49 Billion by 2027 | The Escalating Burden of Chronic Diseases and Genetic Aberrations will be the...

DUBLIN, Feb. 3, 2021 /PRNewswire/ -- The "Precision Medicine Market - Forecasts from 2021 to 2026" report has been added to ResearchAndMarkets.com's offering.

The precision medicine market is evaluated at US$60.422 billion for the year 2020 growing at a CAGR of 8.79% reaching the market size of US$100.168 billion by the year 2026.

Increasing Chronic Diseases

The market is expected to be driven by the growth and surge in several chronic diseases such as cardiovascular diseases, obesity, and other related diseases. According to the World Health Organization, Cardiovascular diseases are one of the major causes of deaths, globally, every year. In 2016, an approx. 17.9 million people died from cardiovascular diseases, which represented approx. 31% of global deaths. Most of these deaths were due to different types of strokes and heart attacks. Precision Medicines have been quickly moving towards real-world clinical features, and various scientific and research organizations, have been looking at different strategies to apply medicine to chronic disease management. Alzheimer's and other related cognitive disorders are among some of the most frequent chronic diseases, which has been making a major impact on individuals, globally. According to the Alzheimer's Association, approx. 5.8 million Americans, have been living with this chronic disease. And, according to the estimation, the number is projected to increase to approx. 14 million, by the year 2050.

There have been various developments in this market when it comes to cognitive disorders. In recent years, Scientists discovered at the University of Buffalo, that a human gene, which is present in 75% of the American population, is one of the major reasons why a section of Alzheimer's Disease medicine or a drug, fails in human studies, despite showing promising results in animal studies. This is expected to be one of the factors in the growth of Precision Medicine, over conventional medicines. Diabetes is also one of the major reasons, which is expected to drive precision market growth. The National Institute of Diabetes and Digestive and Kidney Diseases, made precision medicines and drugs a major priority, for the institute's Diabetes Genomics and Genetics Program. The program has aimed to identify the intergenic regions and genes that provide protection, against type 1 or 2 diabetes.

Other major organizations have also been applying precision medicine techniques and technology for diabetes treatment. Massachusetts General Hospital discovered that the interventions, which had been focussed on individuals' genetic profiles and data, had been able to reduce the risk of type 2 diabetes. The Louisiana Health system performed around 300,000 virtual visits in the year 2020. The health system which is also known as Ochsner Health, provides digital health programs and solutions, to its patients. The Ochsner made substantial investments in the last four years, in developing direct to consumer telemedicine care services and delivery. The Ochsner will also develop telehealth for ICU, psychiatry, and stroke in the next decade.

Precision Medicine In Cancer Treatment

Precision Medicine is also known as personalized medicine, as doctors select this medicine based on a genetic understanding of the patient. The market is expected to be driven by the use of precision medicines for cancer treatment. According to the World Health Organisation, Cancer is the second major cause of death, worldwide. Cancer killed an estimated number of 9.6 million people, in the year 2018. There has been approx. 70% of deaths from cancer, in lower and middle-income countries.

There are several infections caused by cancer such as HPV, Hepatitis B Virus, C virus, and others. Precision medicine could be used to treat cancer, as there are genetic changes constantly occurring in a person's cancer problem. Scientists have been working to identify and conduct genetic tests, which would be used to decide the treatment of a person's cancer or a tumor. In January 2021, Researchers from the John Hopkins Kimmel Cancer Centre, The John Hopkins Departments of Oncology and Pathology, and other 18 organizations around Poland and the United States, compiled a database of neck and head cancers, which would be used to speed up the development and production of precision medicine therapies. With the collected database, the researchers got the clarification of key cancer-associated proteins, genes, which resulted in the advancement in the pathway of these cancers. Precision medicines will also be used for oncology, as major companies have been making developments in advancement and innovation.

In January 2021, Illumina, one of the major players in the market, announced an expanded and novel oncology partnership with Merck, Myriad Genetics, Kura Oncology, Bristol Myers Squibb, to advance a complete and detailed genomic profiling. Genetic sequencing is a major part of precision medicine, and this partnership would result in the advancement of novel and innovative precision medicines.

Current Trends

Key Topics Covered:

1. Introduction1.1. Market Definition1.2. Market Segmentation

2. Research Methodology2.1. Research Data2.2. Assumptions

3. Executive Summary3.1. Research Highlights

4. Market Dynamics4.1. Market Drivers4.2. Market Restraints4.3. Porters Five Forces Analysis4.3.1. Bargaining Power of End-Users4.3.2. Bargaining Power of Buyers4.3.3. Threat of New Entrants4.3.4. Threat of Substitutes4.3.5. Competitive Rivalry in the Industry4.4. Industry Value Chain Analysis

5. Precision Medicine Market Analysis, By Technology5.1. Introduction5.2. Data Analytics5.3. Bioinformatics5.4. Gene Sequencing5.5. Others

6. Precision Medicine Market Analysis, by Application6.1. Introduction6.2. Oncology6.3. Central Nervous System6.4. Immunology6.5. Cardiovascular6.6. Others

7. Precision Medicine Market Analysis, by Geography7.1. Introduction7.2. North America7.2.1. North America Precision Medicine Market, By Technology, 2021 to 20267.2.2. North America Precision Medicine Market, By Application, 2021 to 20267.2.3. By Country7.2.3.1. USA7.2.3.2. Canada7.2.3.3. Mexico7.3. South America7.3.1. South America Precision Medicine Market, By Technology, 2021 to 20267.3.2. North America Precision Medicine Market, By Application, 2021 to 20267.3.3. By Country7.3.3.1. Brazil7.3.3.2. Argentina7.3.3.3. Others7.4. Europe7.4.1. Europe Precision Medicine Market, By Technology, 2021 to 20267.4.2. Europe Precision Medicine Market, By Application, 2021 to 20267.4.3. By Country7.4.3.1.1. Germany7.4.3.1.2. France7.4.3.1.3. UK7.4.3.1.4. Others7.5. Middle East and Africa7.5.1. Middle East and Africa Precision Medicine Market, By Technology, 2021 to 20267.5.2. Middle East and Africa Precision Medicine Market, By Application, 2021 to 20267.5.3. By Country7.5.3.1. Saudi Arabia7.5.3.2. UAE7.5.3.3. Others7.6. Asia Pacific7.6.1. Asia Pacific Precision Medicine Market, By Technology, 2021 to 20267.6.2. Asia Pacific Precision Medicine Market, By Application, 2021 to 20267.6.3. By Country7.6.3.1. China7.6.3.2. India7.6.3.3. Japan7.6.3.4. South Korea7.6.3.5. Others

8. Competitive Environment and Analysis8.1. Major Players and Strategy Analysis8.2. Emerging Players and Market Lucrativeness8.3. Mergers, Acquisitions, Agreements, and Collaborations8.4. Vendor Competitiveness Matrix

9. Company Profiles9.1. Thermo Fisher Scientific Inc.9.2. AstraZeneca plc9.3. F. Hoffmann-La Roche Ltd9.4. Pfizer Inc.9.5. Nordic Bioscience A/S9.6. Medtronic9.7. Novartis AG9.8. QIAGEN9.9. Quest Diagnostics Incorporated9.10. Bristol Myers Squibb

For more information about this report visit https://www.researchandmarkets.com/r/8dixfx

Media Contact:

Research and Markets Laura Wood, Senior Manager [emailprotected]

For E.S.T Office Hours Call +1-917-300-0470 For U.S./CAN Toll Free Call +1-800-526-8630 For GMT Office Hours Call +353-1-416-8900

U.S. Fax: 646-607-1907 Fax (outside U.S.): +353-1-481-1716

SOURCE Research and Markets

http://www.researchandmarkets.com

Originally posted here:
The Worldwide Precision Medicine Industry is Expected to Reach $100 Billion by 2026 - PRNewswire

New findings of breast cancer gene mutations in women who have no family history of the disease offer a new way of estimating risk and may change the way in which these women are advised on risk management.

The findings come from two large studies, both published on January 20 in The New England Journal of Medicine.

The two articles are "extraordinary" for broadening and validating the genomic panel to help screen women at risk for breast cancer in the future, commented Eric Topol, MD, professor of molecular medicine, Scripps Research, La Jolla, California, and Medscape editor-in-chief.

"Traditionally, genetic testing of inherited breast cancer genes has focused on women at high risk who have a strong family history of breast cancer or those who were diagnosed at an early age, such as under 45 years," commented the lead investigator of one of studies, Fergus Couch, PhD, pathologist at the Mayo Clinic, Rochester, Minnesota.

"[Although] the risk of developing breast cancer is generally lower for women without a family history of the disease...when we looked at all women, we found that 30% of breast cancer mutations occurred in women who are not high-risk," he said.

In both studies, mutations or variants in eight genes BRCA1, BRCA2, PALB2, BARD1, RAD51C, RAD51D, ATM, and CHEK2 were found to be significantly associated with breast cancer risk.

However, the distribution of mutations among women with breast cancer differed from the distribution among unaffected women, notes Steven Narod, MD, from the Women's College Research Institute, Toronto, Ontario, Canada, in an accompanying editorial.

"What this means to clinicians, now that we are expanding the use of gene-panel testing to include unaffected women with a moderate risk of breast cancer in the family history, is that our time will increasingly be spent counseling women with CHEK2 and ATM mutations," he writes. Currently these two are "clumped in with 'other genes'.... [M]ost of the pretest discussion is currently focused on the implications of finding a BRCA1 or BRCA2 mutation."

The new findings may lead to new risk management strategies, he suggests. "Most breast cancers that occur in women with a mutation in ATM or CHEK2 are estrogen receptor positive, so these women may be candidates for anti-estrogen therapies such as tamoxifen, raloxifene, or aromatase inhibitors," he writes.

Narod observes that for now, the management of most women with either mutation will consist of screening alone, starting with MRI at age 40 years.

The medical community is not ready yet to expand genetic screening to the general population, cautions Walton Taylor, MD, past president of the American Society of Breast Surgeons (ASBrS).

The ASBrS currently recommends that all patients with breast cancer as well as those at high risk for breast cancer be offered genetic testing. "All women at risk should be tested, and all patients with pathogenic variants need to be managed appropriately it saves lives," Taylor emphasized.

However, "unaffected people with no family history do not need genetic testing at this time," he told Medscape Medical News.

As to what physicians might do to better manage patients with mutations that predispose to breast cancer, Taylor said, "It's surprisingly easy."

Every genetic testing company provides genetic counselors to guide patients through next steps, Taylor pointed out, and most cancer patients have nurse navigators who make sure patients get tested and followed appropriately.

Members of the ASBrS follow the National Comprehensive Cancer Network guidelines when they identify carriers of a pathogenic variant. Taylor says these are very useful guidelines for virtually all mutations identified thus far.

"This research is not necessarily new, but it is confirmatory for what we are doing, and that helps us make sure we are going down the right pathway," Taylor said. "It confirms that what we think is right is right and that matters," he reaffirmed.

The study led by Mayo's Couch was carried out by the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. It involved analyzing data from 17 epidemiology studies that focused on women in the general population who develop breast cancer. For the studies, which were conducted in the United States, pathogenic variants in 28 cancer-predisposition genes were sequenced from 32,247 women with breast cancer (case patients) and 32,544 unaffected women (control persons).

In the overall CARRIERS analysis, the prevalence of pathogenic variants in 12 clinically actionable genes was 5.03% among case patients and 1.63% among control persons. The prevalence was similar in non-Hispanic White women, non-Hispanic Black women, and Hispanic case patients, as well as control persons, they add. The prevalence of pathogenic variants among Asian American case patients was lower, at only 1.64%, they note.

Among patients who had breast cancer, the most common pathogenic variants included BRCA2, which occurred in 1.29% of case patients, followed by CHEK2, at a prevalence of 1.08%, and BRCA1, at a prevalence of 0.85%.

Mutations in BRCA1 increased the risk for breast cancer more than 7.5-fold; mutations in BRCA2 increased that risk more than fivefold, the investigators state.

Mutations in PALB2 increased the risk of breast cancer approximately fourfold, they add.

Prevalence rates for both BRCA1 and BRCA2 among breast cancer patients declined rapidly after the age of 40. The decline in other variants, including ATM, CHEK2, and PALB2, was limited with increasing age.

Indeed, mutations in all five of these genes were associated with a lifetime absolute risk for breast cancer greater than 20% by the age of 85 among non-Hispanic Whites.

Pathogenic variants in BRCA1 or BRCA2 yielded a lifetime risk for breast cancer of approximately 50%. Mutations in PALB2 yielded a lifetime breast cancer risk of approximately 32%.

The risk of having a mutation in specific genes varied depending on the type of breast cancer. For example, mutations in BARD1, RAD51C, and RAD51d increased the risk for estrogen receptor (ER)negative breast cancer as well as triple-negative breast cancer, the authors note, whereas mutations in ATM, CDH1, and CHEK2 increased the risk for ER-positive breast cancer.

"These refined estimates of the prevalences of pathogenic variants among women with breast cancer in the overall population, as opposed to selected high-risk patients, may inform ongoing discussions regarding testing in patients with breast cancer," the BCAC authors observe.

"The risks of breast cancer associated with pathogenic variants in the genes evaluated in the population-based CARRIERS analysis also provide important information for risk assessment and counselling of women with breast cancer who do not meet high-risk selection criteria," they suggest.

The second study was conducted by the Breast Cancer Association Consortium (BCAC) under lead author Leila Dorling, PhD, University of Cambridge, United Kingdom. This group sequenced 34 susceptibility genes from 60,466 women with breast cancer and 53,461 unaffected control persons.

"Protein-truncating variants in 5 genes (ATM, BRCA1, BRCA2, CHEK2 and PALB2) were associated with a significant risk of breast cancer overall (P < .0001)," the BCAC members report. "For these genes, odds ratios ranged from 2.10 to 10.57," they add.

The association between overall breast cancer risk and mutations in seven other genes was more modest, conferring approximately twice the risk for breast cancer overall, although that risk was threefold higher for the TP53 mutation.

For the 12 genes the consortium singled out as being associated with either a significant or a more modest risk for breast cancer, the effect size did not vary significantly between European and Asian women, the authors note. Again, the risk forER-positive breast cancer was over two times greater for those who had either the ATM or the CHEK2 mutation. Having mutations in BARD1, BRCA1, BRCA1, PALB2, RAD51C, and RAD51D conferred a higher risk for ER-negative disease than for ER-positive disease.

There was also an association between rare missense variants in six genes CHEK2, ATM, TP53, BRCA1, CDH1, and RECQL and overall breast cancer risk, with the clearest evidence being for CHEK2.

"The absolute risk estimates place protein-truncating variants in BRCA1, BRCA2, and PALB2 in the high-risk category and place protein-truncating variants in ATM, BARD1, CHEK2, RAD51CC, and RAD51D in the moderate-risk category," Dorling and colleagues reaffirm.

"These results may guide screening as well as prevention with risk-reducing surgery or medication, in accordance with national guidelines," the authors suggest.

The CARRIERS study was supported by the National Institutes of Health. The study by Dorling and colleagues was supported by the European Union Horizon 2020 research and innovation programs, among others. Narod has disclosed no relevant financial relationships.

New Eng J Med. Published online January 20, 2021. Couch et al, Abstract; BCAC study, Full text; Editorial

For more from Medscape Oncology, join us on Twitter and Facebook.

Read more:
Breast Cancer Gene Mutations Found in 30% of All Women - Medscape

Access to industry-leading genomic database and real-world evidence designed to optimize trial design, site selection, clinical trial matching and translational research

BOSTON, MA, DURHAM, NC and FT. MYERS, FL / ACCESSWIRE / February 4, 2021 / Parexel, a leading provider of solutions to accelerate the development and delivery of innovative therapies to improve world health, from clinical through commercialization, and NeoGenomics, Inc. (Acquired By American Communications Enterprises,Inc.(NASDAQ:NEO), a leading provider of cancer-focused genetic testing services and global oncology contract research services, today announced a strategic partnership to advance the application of precision medicine in oncology clinical trials by applying real-world genomics data to accelerate patient matching and optimize trial design, site selection, clinical development and translational research.

The collaboration with NeoGenomics will enhance Parexel's use of real-world data across various applications, including identifying and estimating prevalence of genomic mutations within respective populations, genomic patterning to stratify patients according to novel biomarkers, and use of de-identified patient data to precisely target patient populations. Collectively these data are designed to better inform clinical trial feasibility, enhance patient matching and create a holistic view of the patient journey by linking genomic data with clinical and consumer datasets. The collaboration will ultimately enable researchers to quickly enroll patients with common to rare cancer mutations and connect them to clinical trials providing the best likelihood of potential treatment success.

"Parexel's partnership with NeoGenomics provides access to greater predictive modeling capabilities so that we can rapidly identify specific patients and connect them to clinical trials that provide them with the best potential for treatment, advance our understanding of their disease and identify the drug's effects and potential benefits," said Sy Pretorius, MD, President, Clinical Development and Chief Medical Officer at Parexel. "This collaboration supports our efforts to adopt more novel approaches in the identification of data populations for oncology studies while keeping the patient at the center of everything we do."

"We are thrilled to collaborate with Parexel to provide our robust genomic and clinical database to help match cancer patients to clinical trials and therapies that are precisely targeted to their unique tumor types and genomic biomarkers," said Douglas VanOort, NeoGenomics' Chairman and Chief Executive Officer. "We look forward to our strategic partnership and future opportunities to broaden our relationship based on customer needs in the oncology space."

The strategic partnership between Parexel and NeoGenomics will enable biopharmaceutical customers to make evidence-based decisions regarding trial designs, companion diagnostics and drug repurposing as well as to build external control arms using genomic data, ultimately providing cancer patients access to the most effective therapies when and where they need them. The companies are considering potential opportunities to expand the scope of the partnership, including lab services and biomarker capabilities.

About ParexelParexel supports the development of innovative new medicines to improve the health of patients. We provide services to help life science and biopharmaceutical clients worldwide transform scientific discoveries into new treatments. From clinical trials to regulatory and consulting services to commercial and market access, our therapeutic, technical and functional ability is underpinned by a deep conviction in what we do. Our Oncology Center of Excellence combines our early advisory core services of medical, regulatory, biostatistics and genomic/biomarker expertise with a multi-disciplinary team of oncology experts and key technology platform partnerships to bring your breakthrough treatments to market faster.

Parexel was named "Best Contract Research Organization" in December 2020 by an independent panel for Informa Pharma Intelligence. For more information, visit our website and follow us on LinkedIn, Twitter and Instagram.

About NeoGenomics, Inc.NeoGenomics, Inc. specializes in cancer genetics testing and information services, providing one of the most comprehensive oncology-focused testing menus in the world for physicians to help them diagnose and treat cancer. The Company's Pharma Services Division serves pharmaceutical clients in clinical trials and drug development.

Headquartered in Fort Myers, FL, NeoGenomics operates CAP accredited and CLIA certified laboratories in Fort Myers and Tampa, Florida; Aliso Viejo, Carlsbad and San Diego, California; Houston, Texas; Atlanta, Georgia; Nashville, Tennessee; and CAP accredited laboratories in Rolle, Switzerland, and Singapore. NeoGenomics serves the needs of pathologists, oncologists, academic centers, hospital systems, pharmaceutical firms, integrated service delivery networks, and managed care organizations throughout the United States, and pharmaceutical firms in Europe and Asia.

CONTACTS:ParexelBecky Levine+1 919 271-5151lori.dorer@parexel.com

W2OLindsay LeCain+1 508 259 9521parexelpr@w2ogroup.com

NeoGenomicsDoug Brown+1 239.768.0600 x2539doug.brown@neogenomics.com

SOURCE: NeoGenomics, Inc.

View source version on accesswire.com:https://www.accesswire.com/627830/Parexel-and-NeoGenomics-Announce-Strategic-Collaboration-in-Precision-Medicine-to-Improve-Study-Designs-and-Accelerate-Patient-Matching-in-Oncology-Clinical-Trials

Go here to see the original:
Parexel and NeoGenomics Announce Strategic Collaboration in Precision Medicine to Improve Study Designs and Accelerate Patient Matching in Oncology...

Dublin, Feb. 02, 2021 (GLOBE NEWSWIRE) -- The "Precision Medicine Market - Forecasts from 2021 to 2026" report has been added to ResearchAndMarkets.com's offering.

The precision medicine market is evaluated at US$60.422 billion for the year 2020 growing at a CAGR of 8.79% reaching the market size of US$100.168 billion by the year 2026.

Increasing Chronic Diseases

The market is expected to be driven by the growth and surge in several chronic diseases such as cardiovascular diseases, obesity, and other related diseases. According to the World Health Organization, Cardiovascular diseases are one of the major causes of deaths, globally, every year. In 2016, an approx. 17.9 million people died from cardiovascular diseases, which represented approx. 31% of global deaths. Most of these deaths were due to different types of strokes and heart attacks. Precision Medicines have been quickly moving towards real-world clinical features, and various scientific and research organizations, have been looking at different strategies to apply medicine to chronic disease management. Alzheimer's and other related cognitive disorders are among some of the most frequent chronic diseases, which has been making a major impact on individuals, globally. According to the Alzheimer's Association, approx. 5.8 million Americans, have been living with this chronic disease. And, according to the estimation, the number is projected to increase to approx. 14 million, by the year 2050.

There have been various developments in this market when it comes to cognitive disorders. In recent years, Scientists discovered at the University of Buffalo, that a human gene, which is present in 75% of the American population, is one of the major reasons why a section of Alzheimer's Disease medicine or a drug, fails in human studies, despite showing promising results in animal studies. This is expected to be one of the factors in the growth of Precision Medicine, over conventional medicines. Diabetes is also one of the major reasons, which is expected to drive precision market growth. The National Institute of Diabetes and Digestive and Kidney Diseases, made precision medicines and drugs a major priority, for the institute's Diabetes Genomics and Genetics Program. The program has aimed to identify the intergenic regions and genes that provide protection, against type 1 or 2 diabetes.

Other major organizations have also been applying precision medicine techniques and technology for diabetes treatment. Massachusetts General Hospital discovered that the interventions, which had been focussed on individuals' genetic profiles and data, had been able to reduce the risk of type 2 diabetes. The Louisiana Health system performed around 300,000 virtual visits in the year 2020. The health system which is also known as Ochsner Health, provides digital health programs and solutions, to its patients. The Ochsner made substantial investments in the last four years, in developing direct to consumer telemedicine care services and delivery. The Ochsner will also develop telehealth for ICU, psychiatry, and stroke in the next decade.

Precision Medicine In Cancer Treatment

Precision Medicine is also known as personalized medicine, as doctors select this medicine based on a genetic understanding of the patient. The market is expected to be driven by the use of precision medicines for cancer treatment. According to the World Health Organisation, Cancer is the second major cause of death, worldwide. Cancer killed an estimated number of 9.6 million people, in the year 2018. There has been approx. 70% of deaths from cancer, in lower and middle-income countries.

There are several infections caused by cancer such as HPV, Hepatitis B Virus, C virus, and others. Precision medicine could be used to treat cancer, as there are genetic changes constantly occurring in a person's cancer problem. Scientists have been working to identify and conduct genetic tests, which would be used to decide the treatment of a person's cancer or a tumor. In January 2021, Researchers from the John Hopkins Kimmel Cancer Centre, The John Hopkins Departments of Oncology and Pathology, and other 18 organizations around Poland and the United States, compiled a database of neck and head cancers, which would be used to speed up the development and production of precision medicine therapies. With the collected database, the researchers got the clarification of key cancer-associated proteins, genes, which resulted in the advancement in the pathway of these cancers. Precision medicines will also be used for oncology, as major companies have been making developments in advancement and innovation.

In January 2021, Illumina, one of the major players in the market, announced an expanded and novel oncology partnership with Merck, Myriad Genetics, Kura Oncology, Bristol Myers Squibb, to advance a complete and detailed genomic profiling. Genetic sequencing is a major part of precision medicine, and this partnership would result in the advancement of novel and innovative precision medicines.

Current Trends

Segmentation

By Technology

By Application

By Geography

Key Topics Covered:

1. Introduction1.1. Market Definition1.2. Market Segmentation

2. Research Methodology2.1. Research Data2.2. Assumptions

3. Executive Summary3.1. Research Highlights

4. Market Dynamics4.1. Market Drivers4.2. Market Restraints4.3. Porters Five Forces Analysis4.3.1. Bargaining Power of End-Users4.3.2. Bargaining Power of Buyers4.3.3. Threat of New Entrants4.3.4. Threat of Substitutes4.3.5. Competitive Rivalry in the Industry4.4. Industry Value Chain Analysis

5. Precision Medicine Market Analysis, By Technology5.1. Introduction5.2. Data Analytics5.3. Bioinformatics5.4. Gene Sequencing5.5. Others

6. Precision Medicine Market Analysis, by Application6.1. Introduction6.2. Oncology6.3. Central Nervous System6.4. Immunology6.5. Cardiovascular6.6. Others

7. Precision Medicine Market Analysis, by Geography7.1. Introduction7.2. North America7.2.1. North America Precision Medicine Market, By Technology, 2021 to 20267.2.2. North America Precision Medicine Market, By Application, 2021 to 20267.2.3. By Country7.2.3.1. USA7.2.3.2. Canada7.2.3.3. Mexico7.3. South America7.3.1. South America Precision Medicine Market, By Technology, 2021 to 20267.3.2. North America Precision Medicine Market, By Application, 2021 to 20267.3.3. By Country7.3.3.1. Brazil7.3.3.2. Argentina7.3.3.3. Others7.4. Europe7.4.1. Europe Precision Medicine Market, By Technology, 2021 to 20267.4.2. Europe Precision Medicine Market, By Application, 2021 to 20267.4.3. By Country7.4.3.1.1. Germany7.4.3.1.2. France7.4.3.1.3. UK7.4.3.1.4. Others7.5. Middle East and Africa7.5.1. Middle East and Africa Precision Medicine Market, By Technology, 2021 to 20267.5.2. Middle East and Africa Precision Medicine Market, By Application, 2021 to 20267.5.3. By Country7.5.3.1. Saudi Arabia7.5.3.2. UAE7.5.3.3. Others7.6. Asia Pacific7.6.1. Asia Pacific Precision Medicine Market, By Technology, 2021 to 20267.6.2. Asia Pacific Precision Medicine Market, By Application, 2021 to 20267.6.3. By Country7.6.3.1. China7.6.3.2. India7.6.3.3. Japan7.6.3.4. South Korea7.6.3.5. Others

8. Competitive Environment and Analysis8.1. Major Players and Strategy Analysis8.2. Emerging Players and Market Lucrativeness8.3. Mergers, Acquisitions, Agreements, and Collaborations8.4. Vendor Competitiveness Matrix

9. Company Profiles9.1. Thermo Fisher Scientific Inc.9.2. AstraZeneca plc9.3. F. Hoffmann-La Roche Ltd9.4. Pfizer Inc.9.5. Nordic Bioscience A/S9.6. Medtronic9.7. Novartis AG9.8. QIAGEN9.9. Quest Diagnostics Incorporated9.10. Bristol Myers Squibb

For more information about this report visit https://www.researchandmarkets.com/r/qxh4vs

See the article here:
Insights on the Precision Medicine Global Market to 2027 - Featuring Thermo Fisher Scientific, AstraZeneca & Pfizer Among Others - GlobeNewswire

The breakthroughs made possible by gene editing were shown in the Jan. 6 news that base editing had repaired a genetic defect in lab mice suffering from progeria, a disorder that prematurely ages and kills children born with the mutation.

Most first-generation gene therapies use a hollowed-out virus to carry synthetic versions of a gene into cells. The transferred gene isnt integrated into the cellular DNA, but the cell can still use the instructions to produce functional versions of the missing protein.

Hundreds of such gene-augmentation therapies are in clinical trials. BioMarin Pharmaceutical, UniQure , and Pfizerare each in Phase 3 trials on therapies to treat hemophilia, the bleeding disorder resulting from a mutation in the gene for a blood-clotting protein. Pfizer is also racing Sarepta Therapeuticsto treat Duchenne muscular dystrophy with transferred genes that can produce working versions of a muscle protein that patients cant produce.

Pfizer is making a big bet on these gene-transfer therapies, with three clinical trials that could lead to approvals in the next few years.

These gene-replacement therapies have limitations, however. Their effect wears off as children grow, or in parts of the body with high cell turnover, since transferred genes arent integrated in the genome and are left behind as cells divide. As a result, these expensive treatments might need to be repeated every few years.

Read the original post

See the article here:
Gene transfer therapies are the 'next big thing' in medicine. Here's how gene editing works and the companies behind it - Genetic Literacy Project

Newswise PHILADELPHIAScientists in the Perelman School of Medicine at the University of Pennsylvania have uncovered the molecular causes of a congenital form of dilated cardiomyopathy (DCM), an often-fatal heart disorder.

This inherited form of DCM which affects at least several thousand people in the United States at any one time and often causes sudden death or progressive heart failure is one of multiple congenital disorders known to be caused by inherited mutations in a gene called LMNA. The LMNA gene is active in most cell types, and researchers have not understood why LMNA mutations affect particular organs such as the heart while sparing most other organs and tissues.

In the study, published this week in Cell Stem Cell, the Penn Medicine scientists used stem cell techniques to grow human heart muscle cells containing DCM-causing mutations in LMNA. They found that these mutations severely disrupt the structural organization of DNA in the nucleus of heart muscle cells but not two other cell types studied leading to the abnormal activation of non-heart muscle genes.

Were now beginning to understand why patients with LMNA mutations have tissue-restricted disorders such as DCM even though the gene is expressed in most cell types, said study co-senior author Rajan Jain, MD, an assistant professor of Cardiovascular Medicine and Cell and Developmental Biology at the Perelman School of Medicine.

Further work along these lines should enable us to predict how LMNA mutations will manifest in individual patients, and ultimately we may be able to intervene with drugs to correct the genome disorganization that these mutations cause, said study co-senior author Kiran Musunuru, MD, PhD, a professor of Cardiovascular Medicine and Genetics, and Director of the Genetic and Epigenetic Origins of Disease Program at Penn Medicine.

Inherited LMNA mutations have long puzzled researchers. The LMNA gene encodes proteins that form a lacy structure on the inner wall of the cell nucleus, where chromosomes full of coiled DNA are housed. This lacy structure, known as the nuclear lamina, touches some parts of the genome, and these lamina-genome interactions help regulate gene activity, for example in the process of cell division. The puzzle is that the nuclear lamina is found in most cell types, yet the disruption of this important and near-ubiquitous cellular component by LMNA mutations causes only a handful of relatively specific clinical disorders, including a form of DCM, two forms of muscular dystrophy, and a form of progeria a syndrome that resembles rapid aging.

To better understand how LMNA mutations can cause DCM, Jain, Musunuru, and their colleagues took cells from a healthy human donor, and used the CRISPR gene-editing technique to create known DCM-causing LMNA mutations in each cell. They then used stem cell methods to turn these cells into heart muscle cells cardiomyocytes and, for comparison, liver and fat cells. Their goal was to discover what was happening in the mutation-containing cardiomyocytes that wasnt happening in the other cell types.

The researchers found that in the LMNA-mutant cardiomyocytes but hardly at all in the other two cell types the nuclear lamina had an altered appearance and did not connect to the genome in the usual way. This disruption of lamina-genome interactions led to a failure of normal gene regulation: many genes that should be switched off in heart muscle cells were active. The researchers examined cells taken from DCM patients with LMNA mutations and found similar abnormalities in gene activity.

A distinctive pattern of gene activity essentially defines what biologists call the identity of a cell. Thus the DCM-causing LMNA mutations had begun to alter the identity of cardiomyocytes, giving them features of other cell types.

The LMNA-mutant cardiomyocytes also had another defect seen in patients with LMNA-linked DCM: the heart muscle cells had lost much of the mechanical elasticity that normally allows them to contract and stretch as needed. The same deficiency was not seen in the LMNA-mutant liver and fat cells.

Research is ongoing to understand whether changes in elasticity in the heart cells with LMNA mutations occurs prior to changes in genome organization, or whether the genome interactions at the lamina help ensure proper elasticity. Their experiments did suggest an explanation for the differences between the lamina-genome connections being badly disrupted in LMNA-mutant cardiomyocytes but not so much in LMNA-mutant liver and fat cells: Every cell type uses a distinct pattern of chemical marks on its genome, called epigenetic marks, to program its patterns of gene activity, and this pattern in cardiomyocytes apparently results in lamina-genome interactions that are especially vulnerable to disruption in the presence of certain LMNA mutations.

The findings reveal the likely importance of the nuclear lamina in regulating cell identity and the physical organization of the genome, Jain said. This also opens up new avenues of research that could one day lead to the successful treatment or prevention of LMNA-mutations and related disorders.

Other co-authors of the study were co-first authors Parisha Shah and Wenjian Lv; and Joshua Rhoades, Andrey Poleshko, Deepti Abbey, Matthew Caporizzo, Ricardo Linares-Saldana, Julie Heffler, Nazish Sayed, Dilip Thomas, Qiaohong Wang, Liam Stanton, Kenneth Bedi, Michael Morley, Thomas Cappola, Anjali Owens, Kenneth Margulies, David Frank, Joseph Wu, Daniel Rader, Wenli Yang, and Benjamin Prosser.

Funding was provided by the Burroughs Wellcome Career Award for Medical Scientists, Gilead Research Scholars Award, Pennsylvania Department of Health, American Heart Association/Allen Initiative, the National Institutes of Health (DP2 HL147123, R35 HL145203, R01 HL149891, F31 HL147416, NSF15-48571, R01 GM137425), the Penn Institute of Regenerative Medicine, and the Winkelman Family Fund for Cardiac Innovation.

###

Penn Medicineis one of the worlds leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of theRaymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nations first medical school) and theUniversity of Pennsylvania Health System, which together form a $8.6 billion enterprise.

The Perelman School of Medicine has been ranked among the top medical schools in the United States for more than 20 years, according toU.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $494 million awarded in the 2019 fiscal year.

The University of Pennsylvania Health Systems patient care facilities include: the Hospital of the University of Pennsylvania and Penn Presbyterian Medical Centerwhich are recognized as one of the nations top Honor Roll hospitals byU.S. News & World ReportChester County Hospital; Lancaster General Health; Penn Medicine Princeton Health; and Pennsylvania Hospital, the nations first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.

Penn Medicine is powered by a talented and dedicated workforce of more than 43,900 people. The organization also has alliances with top community health systems across both Southeastern Pennsylvania and Southern New Jersey, creating more options for patients no matter where they live.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2019, Penn Medicine provided more than $583 million to benefit our community.

View post:
Stem Cell Study Illuminates the Cause of a Devastating Inherited Heart Disorder - Newswise

Excitement took wing in the scientific community in the early 1990s, when the first gene therapy trial showed significant success, only to crash at the end of the decade with a patients tragic death.

Twenty years later, the excitement is back and greater than before. Although safety remains a concern, investigators are breaking ground in cell and gene therapy, and many believe that ultimately, a string of cured cancers will follow.

In 2017, the excitement over these therapies returned in spades when the FDA signed off on a cell-therapy drug for the first time, approving the chimeric antigen receptor (CAR) T-cell treatment tisagenlecleucel (Kymriah; Novartis) for patients with B-cell precursor acute lymphoblastic leukemia. At last, scientists had devised a way to reprogram a persons own T cells to attack tumor cells.

Were entering a new frontier, said Scott Gottlieb, MD, then-FDA commissioner, in announcing the groundbreaking approval.

Gottlieb was not exaggerating. The growth in CAR T-cell research is exploding. Although only a handful of cell and gene therapies are on the market, the FDA predicted in 2019 that it will receive more than 200 investigational new drug applications per year for cell and gene therapies, and that by 2025, it expects to have accelerated to 10 to 20 cell and gene therapy approvals per year.

We can absolutely cut the number of cancer deaths down so that one day in our lifetimes it can be a rare thing for people to die of cancer, said Patrick Hwu, MD, president and CEO of Moffitt Cancer Center in Florida and among gene therapys pioneers. It still may happen here and there, but itll be kind of like people dying of pneumonia. Its like, He died of pneumonia? Thats kind of weird. I think cancer can be the same way.

Essentially, you can kill any cancer cell that has an antigen that is recognized by the immune cell, Hwu said. The key to curing every single cancer, which is our goal, is to have receptors that can recognize the tumor but dont recognize the normal cells.

Community oncologists will need to be increasingly familiar about the various products, including their immediate and longer-term risks, Bo Wang, MD, and Deepu Madduri, MD, recently wrote in OncologyLive.1 It is key to understand the optimal time for referring these patients to an academic institution, as well as how to manage the requisite post CAR T-cell therapy in the community setting. Madduri is an assistant professor of medicine, hematology and medical oncology, as well as associate director of cellular therapy service, and director of clinical operations with the Center of Excellence for Multiple Myeloma at The Tisch Cancer Institute and the Icahn School of Medicine at Mount Sinai in New York, New York. Wang is a third-year clinical fellow in hematology/oncology at Mount Sinai.

Early referral to academic centers and hospitals equipped to deliver therapies is crucial for patients eligible for therapy. However, as advances continue in the field, community practices may be called upon to administer therapies in their clinic.

The Community Oncology Alliance (COA) envisions a broader role for the settings in which CAR T-cell therapies can be administered. When the Centers for Medicare & Medicaid Services (CMS) was considering coverage for CAR T-cell therapies in 2019, COA officials argued against limiting approvals to hospitals.

It is important to understand that there are state-of-the-art community oncology practices that have significant experience and capabilities in administering highly complex treatments, COA officials wrote in a letter to CMS. For example, stem cell transplants, which are similar in complexity to CAR T therapy, are performed successfully in the community oncology practice setting.2

Broader use of gene therapies depends on several factors, including navigating the logistics of gene therapies, addressing the high costs, and managing toxicities.3

Autologous CAR T-cell therapies involve a manufacturing process that requires coordination between the treating facility and the processing facility. Following leukapheresis, patients may require maintenance therapy to control disease progression during the manufacturing time, which can take 3 to 5 weeks.

In terms of cost, gene and cell therapies can cost from $375,000 to $475,000 per dose and they may face coverage restrictions from payers. Approvals could take weeks to obtain.3,4

Because of cytokine release syndrome and neurotoxicities associated with CAR T-cell therapy, the FDA mandates risk evaluation and mitigation strategy training for centers.

Further, providers may find that real-world experiences with gene therapies are different from those seen in the clinical trial setting, according to Ankit J. Kansagra, MD.

In a presentation at the 2020 American Society of Clinical Oncology Virtual Education Program, Kansagra, an assistant professor of medicine and Eugene P. Frenkel, MD, Scholar in Clinical Medicine at Harold C. Simmons Comprehensive Cancer Center in Dallas, Texas, said that in practice patients may be older and have more aggressive disease, with double- and triple-hit lymphomas.4

Specifically, Kansagra noted that medications such as steroids and/or tocilizumab (Actemra) to prevent or treat cytokine release syndrome or other toxicities were more frequently used in the real-world setting than what had been seen in clinical trials.

As it stands now, only a fraction of eligible patients are receiving CAR T-cell therapies, Kansagra said. Potentially, 9750 patients a year may be eligible for CAR T-cell therapies in approved and upcoming hematologic indications. From 2016 to 2019, a total of 2058 patients received CAR T-cell infusion.4

Next steps for transplanting these novel therapies to clinical practice will require changes in key areas, Kansagra said, such as supply chain management, patient support, and financial systems (Figure).4

Figure. Next Steps for Effective Delivery of Gene and Cell Therapies4

Meanwhile, multiple myeloma experts advise providers to be ready for change. As commercially available myeloma CAR T-cell therapies are approved, it will be even more important for community oncologists to better understand these therapies so they can offer them to their patients, Wang and Madduri wrote.1

Cell therapy involves cultivating or modifying immune cells outside the body before injecting them into the patient. Cells may be autologous (self-provided) or allogeneic (donor-provided); they include hematopoietic stem cells and adult and embryonic stem cells. Gene therapy modifies or manipulates cell expression. There is considerable overlap between the 2 disciplines.

Juliette Hordeaux, PhD, senior director of translational research for the University of Pennsylvanias gene therapy program, is cautious about the FDAs predictions, saying shed be thrilled with 5 cell and/or gene therapy approvals annually.

For monogenic diseases, there are only a certain number of mutations, and then well plateau until we reach a stage where we can go after more common diseases, Hordeaux said.

Safety has been the main brake around adeno-associated virus vector [AAV] gene therapy, added Hordeaux, whose hospitals program has the institutional memory of both Jesse Gelsingers tragic death during a 1999 gene therapy trial as well as breakthroughs by 2015 Giants of Cancer Care winner in immuno-oncology Carl H. June, MD, and others in CAR T-cell therapy. Sometimes there are unexpected toxicity [events] in trials.I think figuring out ways to make gene therapy safer is going to be the next goal for the field before we can even envision many more drugs approved.

In total, 3 CAR T-cell therapies are now on the market, all targeting the CD19 antigen. Tisagenlecleucel was the first. Gilead Sciences received approval in October 2017 for axicabtagene ciloleucel (axi-cel; Yescarta), a CAR T-cell therapy for adults with large B-cell non-Hodgkin lymphoma. Kite Pharma, a subsidiary of Gilead, received an accelerated approval in July 2020 for brexucabtagene autoleucel (Tecartus) for adults with relapsed/ refractory mantle cell lymphoma.

Another CD19-directed therapy under FDA review for relapsed/refractory large B-cell lymphoma, is lisocabtagene maraleucel (liso-cel; JCAR017; Bristol Myers Squibb). Idecabtagene vicleucel (ide-cel; bb2121; Bristol Myers Squibb) is under priority FDA review, with a decision expected by March 31, 2021. The biologics license application for ide-cel seeks approval for the B-cell maturation antigendirected CAR therapy to treat adult patients with multiple myeloma who have received at least 3 prior therapies.5

The number of clinical trials evaluating CAR T-cell therapies has risen sharply since 2015, when investigators counted a total of 78 studies registered on the ClinicalTrials. gov website. In June 2020, the site listed 671 trials, including 357 registered in China, 256 in the United States, and 58 in other countries.6 Natural killer (NK) cells are the research focus of Dean A. Lee, MD, PhD, a physician in the Division of Hematology and Oncology at Nationwide Childrens Hospital in Columbus, Ohio. He developed a method for consistent, robust expansion of highly active clinical-grade NK cells that enables repeated delivery of large cell doses for improved efficacy. This finding led to several first-in-human clinical trials evaluating adoptive immunotherapy with expanded NK cells under an FDA investigational new drug application. Lee is developing both genetic and nongenetic methods to improve tumor targeting and tissue homing of NK cells. His efforts are geared toward pediatric sarcomas.

The biggest emphasis over the past 20 to 25 years has been cell therapy for cancer, talking about trying to transfer a specific part of the immune system for cells, said Lee, who is also director of the Cellular Therapy and Cancer Immunology Program at Nationwide Childrens Hospital, at The Ohio State University Comprehensive Cancer Center Arthur G. James Cancer Hospital, and at the Richard J. Solove Research Institute.

However, Lee said, NKs have wider potential. This is kind of a natural swing back. Now that we know we can grow them, we can reengineer them against infectious disease targets and use them in that [space], he said.

Lee is part of a coronavirus disease 2019 (COVID-19) clinical trial, partnering with Kiadis, for off-the-shelf K-NK cells using Kiadis proprietary platforms. Such treatment would be a postexposure preemptive therapy for treating COVID-19. Lee said the pivot toward treating COVID19 with cell therapy was because some of the very early reports on immune responses to coronavirus, both original [SARS-CoV-2] and the new [mutation], seem to implicate that those who did poorly [overall] had poorly functioning NK cells.

The revolutionary gene editing tool CRISPR is making its initial impact in clinical trials outside the cancer area. Its developers, Jennifer Doudna, PhD, and Emmanuelle Charpentier, PhD, won the Nobel Prize in Chemistry 2020.

For patients with sickle cell disease (SCD), CRISPR was used to reengineer bone marrow cells to produce fetal hemoglobin, with the hope that the protein would turn deformed red blood cells into healthy ones. National Public Radio (NPR) did a story on one patient who, so far, thanks to CRISPR, has been liberated from the attacks of SCD that typically have sent her to the hospital, as well from the need for blood transfusions.7

Its a miracle, you know? the patient, Victoria Gray of Forest, Mississippi, told NPR.

She was among 10 patients with SCD or transfusion-dependent beta-thalassemia treated with promising results, as reported by the New England Journal of Medicine.8

Stephen Gottschalk, MD, chair of the department of bone marrow transplantation and cellular therapy at St Jude Childrens Research Hospital, said, Theres a lot of activity to really explore these therapies with diseases that are much more common than cancer.

Animal models use T cells to reverse cardiac fibrosis, for instance, Gottschalk said. Using T cells to reverse pathologies associated with senescence, such as conditions associated with inflammatory clots, are also being studied.

CAR T, I think, will become part of the standard of care, Gottschalk said. The question is how to best get that accomplished. To address the tribulations of some autologous products, a lot of groups are working with off-the-shelf products to get around some of the manufacturing bottlenecks. I believe those issues will be solved in the long run.

See original here:
Harnessing the Potential of Cell and Gene Therapy - OncLive