Santoro, Jonathan Douglas MD

This new R25 program, responsive to PAR-22-195, plays a crucial role in the INCLUDE project (Investigation of Co-occurring conditions across the Lifespan to Understand Down syndromE). Each year, we recruit,train, mentor, and provide career advice to a cohort of 16 post-graduate participants dedicated to mastering Down syndrome (DS) clinical research. Despite the swift growth of INCLUDE, there are still too few laboratories led by Down syndrome expert scientists and too few new clinical trainees with expertise in Down Syndrome. In full compliance with NOT-OD-25-090 (Notice of Civil Rights Term and Condition of Award), this program is available for all qualified American Citizens and Permanent Residents. Under the direction of multiple Principal Investigators, Ann Cohen, PhD (Pitt); Benjamin Handen, PhD (Pitt); Elizabeth Head, PhD (Irvine); Adam Resnick, MD, PhD (CHOP); Jonathan Santoro, MD (USC-Keck); and Gerald Schatten, PhD (Contact PI, Pitt), with Co-Investigator Calvin Simerly, PhD (Pitt), the ICRT initiative proposes five specific aims: I. Annual ICRT courses covering DS through the entire lifespan; II. Ongoing Mentoring; III. Fostering Intra-INCLUDE Collaborations and Partnerships; IV. Responsible Conduct for Research training to ensure full compliance with NIH and Institutional guidance, regulations and law; and V. Quantitative Independent Evaluations to track Participants’ Careers, comprehensively and longitudinally, to ensure that ICRT is a wise, effective investment. ICRT will meet and exceed the PAR’s mandate of training the next generation of DS clinical researchers, 80 additional clinical investigators, and thereby improving the quality of life and health span of those with Down syndrome.

Among the many co-occurring conditions that can affect individuals with Down syndrome, the neurological condition known as Down Syndrome Regression Disorder (DSRD) is undoubtedly one of the most detrimental, including symptoms such as catatonia, mutism, depersonalization, loss of ability to perform activities of daily living, hallucinations, delusions, and aggression. This project consists of a research-intensive clinical trial to compare the relative safety and efficacy of three alternative therapeutic approaches in DSRD, including two promising immune-modulatory medicines. Results from this project will produce much needed information about the etiology of DSRD and its response to diverse interventions.

Down syndrome (DS) is one of the most common genetic disorders with a prevalence of 1 per 700 liveborn infants in the United States and is associated with an increased risk of developing cerebrovascular disorders (CeVD), which commonly present with stroke as the first evidence of disease. The proposed research will result in the creation of a validated, non-invasive, low-cost, biometric screening tool for young persons with DS in order to address the pressing need of reliable screening of CeVD in at-risk individuals. This proposal presents a five-year research career development program with training that will position me with a unique set of interdisciplinary skills to enable transition to independence as a physician-scientist to study the prediction and prevention of CeVD in persons with DS.