CERSI Collaborators: Stanford University: Joseph Wu, MD, PhD; John Day, MD, PhD
FDA Collaborators: Center for Drug Evaluation and Research: David Strauss, MD, PhD; Rodney Rouse, DVM; Kevin Ford, PhD
Project Start Date: October 2022
Regulatory Science Challenge
Assessing drug safety and efficacy for rare diseases remains a challenge. The different changes in genes that occur in rare diseases may alter the effects of a drug. Also, since there are few patients with rare diseases, enrolling patients with rare diseases in human clinical studies can be challenging. Failure is expensive: if a drug cannot be evaluated in humans, or does not work to treat the disease, it means the drug sponsor loses both the money and the time invested in drug development, and patients remain without treatment options. However, cell-based models offer the opportunity to fill information gaps. For example, the FDA recently expanded approved patient populations for treatments for two rare diseases (cystic fibrosis and Fabry disease) based on cellular data.
Project Description and Goals
Researchers will aim to build and test a human disease-specific cell model to conduct clinical research in a dish for rare diseases. In this study, researchers will use Duchenne Muscular Dystrophy (DMD) as an example of a rare disease. Researchers will modify the blood cells from several DMD patients into pluripotent stem cells, which are cells that can become different cell types, such as heart and skeletal muscles. Once researchers have these different cell types in a dish, they will assess if the cells correspond to the patient’s clinical features and test the cells’ responses to drugs.
Researchers also will conduct studies on healthy cells that have had their genomes edited to mimic those genetic changes seen in DMD. As part of such a process, researchers will test whether the changes reliably capture the patient’s DMD phenotypes and drug response. Different changes in genes can be edited separately into this same healthy cell line for comparison. This research will provide information on the potential future use of these technologies to replace, reduce, or refine clinical trials for rare diseases.