Clinical Research Studies

Our ultimate goal is to develop new treatments for patients with familial dysautonomia (FD, OMIM 223900). We also want to learn which specific nerve populations are affected by the disease-causing mutation, whether these features are progressive, and how best to measure them in clinical trials. FD is caused by a founder mutation in the IKBKAP gene that is carried by 1:30 people of European Jewish ancestry. Over 99% of affected patients have two copies of the identical founder mutation. This affects the development of the sensory nervous system, which relays information to the brain. FD is both developmental and progressive. Current drug treatments are supportive and none specifically target the on-going neurological decline. Partnership between academic centers, advocacy groups and federal agencies has allowed the creation of a pipeline for drug development and an infrastructure for translational research. The first aim of this project will be to enroll patients with FD from around the world in a non-interventional natural history study. We will score the severity of their clinical features and follow how they evolve over time. The natural history will focus on establishing disease-specific milestones to use as outcome measures in future clinical trials. We will find ways to measure the progressive neurological aspects of the disease including blindness and gait ataxia, which are intrinsically related and most devastating to the patient’s quality of life overtime. We will also explore other potential biomarkers that quantify renal, cardiovascular, respiratory, orthopedic and cognitive aspects of the disease, which will help us monitor adverse events. The second aim of this project will address one of the most intriguing questions about the disease; why some patients are more severely affected than others. The study will include genomic sequencing from patients with FD, to find specific modifier genes that influence the severity of traits as possible targets for future drug development. Some of these genes may be important in the general population, but discovering them could be easier in FD patients due to >99% being homozygous for the founder mutation.