The Bespoke Gene Therapy Consortium (BGTC) is part of the Accelerating Medicines Partnership® (AMP®) program, a public-private partnership between the NIH, the US Food and Drug Administration (FDA), several pharmaceutical and life science companies, as well as nonprofits and other organizations. The AMP program, administered by the Foundation for the NIH (FNIH), aims to improve current models for developing diagnostics and therapies. The BGTC is establishing platforms and standards to accelerate the development and delivery of bespoke or “bespoke” gene therapies that could treat millions of people affected by rare diseases, including diseases too rare to be commercially available Interest to be. The BGTC is the first AMP initiative to focus on rare diseases and the sixth AMP initiative overall. It is also the first to focus on a therapeutic platform.
Rare Diseases and the Promise of Gene Therapy
3D rendering of genetic medicine with isolated DNA. (xsense / Shutterstock)
Approximately 7,000 known diseases are classified as “rare,” which means that each one affects fewer than 200,000 people in the United States. Overall, rare diseases are rarely rare; 25-30 million people in the United States have rare diseases that affect their quality of life and threaten their health. In addition, they have significantly higher medical costs, with medical care for people with rare diseases being three to five times higher than for people without rare diseases.
Less than 10% of rare diseases have FDA approved treatments. About 80% of rare diseases are caused by known changes in a single gene. This common characteristic makes these diseases potential candidates for gene therapy in which a defective gene is replaced or corrected. However, developing gene therapies for rare diseases is complex, time consuming and expensive. The gene therapy development process is hampered by a lack of access to proprietary tools and methods, a lack of standards and a disease-specific approach. As of December 2021, only two rare diseases have FDA-cleared gene therapy.
The consortium for bespoke gene therapy
Launched in October 2021, BGTC will generate gene therapy resources that the research community can use to streamline gene therapy development for rare diseases and make the process more efficient and cost effective.
One of the goals of the BGTC is to improve understanding of the basic biology of the harmless adeno-associated virus (AAV), a widely used vehicle or vector for gene delivery. BGTC scientists will learn more about how AAVs transport genes to the right place in cells, how these genes get into the cells and how the newly transported genes are activated in the target cells. This information will help improve the effectiveness of AAV gene therapies.
Another important goal of BGTC is to improve the efficiency of both vector manufacture and production quality control tests. The BGTC will accomplish this by developing a standardized and widely applicable set of analytical tests that can be used to produce viral vectors.
The clinical component of the BGTC aims to simplify the path from animal experiments to human tests. Funded researchers will conduct between four and six clinical studies, with each study focusing on a different rare disease. None of the diseases selected will have an existing gene therapy or one in development, but the diseases selected will be well understood and the funded scientists will have considerable experience researching each disease. In addition, various AAV vectors that have already been used in other studies are used in the studies. During the BGTC clinical trials, scientists will develop strategies to streamline regulatory processes for FDA approval of safe and effective gene therapies and develop standardized approaches for preclinical testing (e.g. toxicological studies).
The role of NCATS
NCATS works with the FDA and FNIH, 10 NIH institutes and centers (ICs), 10 pharmaceutical companies, and 5 nonprofits to create the BGTC. NCATS, the lead NIH IC for BGTC, expects approximately $ 8 million of the total of $ 39.5 million to be contributed by participating NIH ICs. Together, the NIH and private partners will contribute approximately $ 76 million to support BGTC-funded projects over a period of 5 years.
NCATS ‘mission is to reshape the translational research process so that new treatments and cures for disease can be delivered to patients more quickly. In particular, NCATS focuses on the critical and unmet needs of people with rare diseases. BGTC is one of several NCATS-led programs applying the “many diseases at once” approach to the development of gene therapies for rare diseases, including the Platform Vector Gene Therapy (PaVe-GT) pilot. Both the PaVe-GT pilot project, which started in February 2019, and the BGTC are working to improve the efficiency and accessibility of the development and delivery of gene therapies for rare diseases. These two efforts serve different but complementary goals, with the PaVe-GT pilot using AAV vectors to develop gene therapies for four rare genetic diseases that differ from the four to six clinical trials supported by the BGTC.
The NCATS intramural laboratories will play an important role in the basic biological component of the BGTC. With expertise in preclinical drug development – including assay development, high throughput screening, disease modeling, toxicity testing, and more – NCATS researchers are poised to generate data that could lead to improved vector production and therapeutic gene activity.
To learn more about the BGTC, including research opportunities, please visit the FNIH website or contact PJ Brooks, Ph.D. from NCATS.