Regenerative Medicine: A New Frontier
A course requirement for BME 274, Regulatory, Clinical & Manufacturing Aspects of Medical Devices taught by Professor Folarin Erogbogbo (Prof. Eros). Please feel free to provide any feedback. #BME274 #SJSU #ProfEros
Gene therapies represent a new frontier in medicine. This technology, also sometimes referred to as regenerative or personalized medicine takes advantage of special delivery vectors such as DNA tumor viruses. These microscopic viruses infect target cells and are able to modify the genes they contain in a beneficial way. The potential benefit of this kind of treatment, is that it uses the patient’s own cells (often immune cells) to fight the issue within the body. This kind of “cellular reprogramming” has had tremendous results in fighting cancers and some genetic diseases. Recently, AveXis (a subsidiary of Novartis) made history as it became the first company to bring a gene therapy to the U.S. market. Zolgensma? (onasemnogene abeparvovec-xioi) was approved in May 2019 to treat a rare and severe form of spinal muscular dystrophy. The treatment is approved for use in children under the age of 2 and provides some physical relief to those that suffer from this terrible affliction. Remarkably, this product is directed to be delivered intravenously in a 60-min continuous infusion only one time. After this single treatment, spinal muscular dystrophy patients are able to make a critical muscular protein needed for proper muscle development.
CRISPR Technology
Scientists are incredibly excited about a new technology that has the ability to change regenerative medicine forever. CRISPR-Cas9 was a system initially characterized in bacteria; biologists soon discovered it is a defense mechanism used by microbes to fight viral infection. They were also able to realize the potential hidden within this ingenious system for excising foreign DNA. A set of proteins is able to precisely cut and “edit” the genome by recognizing a set of clustered randomly interspersed palindromic repeats in a DNA sequence. This new technology is rapidly adapting to the field of regenerative medicine. This tool could be used in the future to treat a myriad of genetic diseases. While this technology is still evolving, it’s long term effects have to be properly studied. It is unclear how cells will behave many years after modification, and little is known about repeated treatments and their effectiveness. More is being uncovered about these incredible developments in medical science every day.
Regulations and Guidance
Next generation treatments are specifically addressed in Section 3034 of the 21st Century Cures Act. The Cures Act specifically refers to Regenerative Medicine Advanced Therapies (RMAT) in section 506(g) of the Federal Food, Drug and Cosmetic Act (FD&C Act 21 U.S.C. 356(g)). The FDA provides any entity attempting to bring a cellular/gene therapy to market with guidance documents and clear directions for how these products can be approved for sale. Although most of these therapies are so new they require de novo classification approval, guidance is also issued for the 510(k) process, Premarket approval (PMA) and humanitarian exemption (HDE) process. RMAT are also regulated under 21 CFR 3.2(e) which applies to combination medical devices; products that are a combination of some pharmaceutical therapy with a physical device. Regenerative medicine becomes increasingly feasible as we discover more about the human genome and learn new ways to manipulate it. To ensure this technology is safe and effective, and that the benefits outweigh the risks, scientists should carefully follow any and all guidance issued by the FDA.