Jay Vivian, PhD
Director, Rare Disease Model Research Program; Scientific Director, Genetically Engineered Mouse Models Core; Associate Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Research Associate Professor of Pathology, University of Kansas School of Medicine
Full BiographyJay Vivian, PhD, Clinical Genetics, along with Scott Weir, MD, PharmD, University of Kansas Medical Center, received a two-year, $449,952 R21 grant from National Institutes of Health (NIH)’s National Center for Advancing Translational Sciences (NCATS). The funding is being used for their project, “Assessment of Everolimus as a Therapy for Vici Syndrome in a Preclinical Model,” which furthers Dr. Vivian’s research on potential therapeutics for Vici syndrome (VS). The grant covers a project period of May 1, 2026-April 30, 2028 (Award No. 1R21TR005180-01A1).
VS is a rare pediatric neurological disorder, more specifically known as a congenital disorder of autophagy. Children with VS can experience significant developmental delays, seizures, immunodeficiency, heart failure and loss of motor function. VS is caused by defects in the EPG5 gene, which encodes a protein used in autophagy — a process where materials within our cells are identified, broken down and recycled. Defects in this gene are associated with VS as well as rare early onset forms of Parkinson’s disease.
While there are no treatment options for pediatric patients with VS, Dr. Vivian’s preclinical findings in patient-derived cellular models showed the FDA-approved drug, everolimus, may be a potential treatment for VS. The study team has found that rapamycin-related class of compounds (rapalogs) like everolimus are autophagy enhancers in VS patient cells. Dr. Vivian hypothesizes that autophagy enhancers are potentially effective treatments for VS.
“We have been fortunate to work closely with VS families to obtain the critical patient cells and genetic information to advance our preclinical studies,” said Dr. Vivian.
This study will test Dr. Vivian’s hypothesis by using preclinical models with VS to analyze the pharmacokinetics and pharmacodynamics of everolimus and assess whether this treatment could cure or slow the progression of the disease. The study team will also analyze neurological function and inflammatory responses while models are undergoing everolimus treatment. This study aims to bridge the gap in knowledge on potential therapeutics and discover an effective treatment option for VS patients.
“This exciting NCATS grant is specifically geared to advance the use of validated preclinical models to verify a candidate therapy and then accelerate translation to clinical trials,” said Dr. Vivian. “We believe this work will have broader impact beyond treatment for VS, including other related congenital disorders of autophagy and neurodegenerative disorders such as Parkinson’s disease.”
Brooke Fridley, PhD, Health Services and Outcomes Research, will serve as a co-investigator on this study.
The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.