Gene Therapy Approach with Liver Hepatocytes
Gene Therapy Approach with Liver Hepatocytes
Research Summary
Drs. Jefferson Doyle, David Valle and Mandeep Singh
Wilmer Eye Institute, Johns Hopkins University
July 2022 | $50,000
In the summer of 2022, Conquering Gyrate Atrophy awarded $50,000 to the Wilmer Eye Institute and Department of Genetics, Johns Hopkins University to support research towards developing gene therapy to slow or reverse the progression of gyrate atrophy. The research will test the possibility of halting or reversing disease progression through delivery of the correct copy of the human OAT gene to liver hepatocytes in animal models with the goal of lower circulating levels of ornithine in the blood. The efficacy of the treatment will be tested in a mouse model of gyrate atrophy, using adeno-associated virus vectors targeting the hepatocytes.
Researcher Profiles
Dr. Doyle is an Assistant Professor of Ophthalmology and Genetics. He completed medical school at Oxford and Cambridge Universities in the U.K., and a PhD in cellular and molecular medicine at Johns Hopkins. He undertook a residency in ophthalmology at Johns Hopkins’ Wilmer Eye Institute, and a fellowship in pediatric ophthalmology at Boston Children’s Hospital, Harvard Medical School. He holds faculty appointments in Wilmer, the Department of Genetic Medicine (DGM) and the Cellular and Molecular Medicine graduate training program. He is a board-certified pediatric ophthalmologist who specializes in the care of patients with genetic disorders that affect the eye, including inherited retinal dystrophies (IRDs). He is co-Director of the Wilmer Genetic Eye Disease Center (GEDI) and oversees the pediatric ERG and VEP services. His research interests include the development of novel therapeutics for genetic eye issues, including gene therapy for IRDs and monogenic high myopia.
Dr. Valle is a Professor in the Department of Genetic Medicine with secondary appointments in pediatrics, medicine and ophthalmology at Johns Hopkins School of Medicine. He is board-certified in clinical molecular genetics, clinical biochemical genetics, clinical genetics and pediatrics. He is the founding Director of the Johns Hopkins Center for Inherited Disease Research and Director of the Predoctoral Training Program in Human Genetics at Johns Hopkins. He is a member of the National Academy of Medicine and has made multiple seminal discoveries regarding gyrate atrophy (GA). He is a world leader on gyrate atrophy and was the first to show that deficiency of OAT is the causative biochemical defect in GA and the first to report causative mutations in the OAT gene. He has personally overseen the metabolic management of more than 50 patients with GA. His laboratory generated the first mouse model of GA, confirmed that it developed chorioretinal degeneration, and demonstrated that an arginine-restricted diet (ARD) could prevent disease progression. He has served as lead or co-author on many clinical publications about GA, including demonstration that an ARD is therapeutically beneficial in patients with GA. Most recently, he has become co-Chair of the GYROS natural history study with Dr. Singh and was the first to show that deficiency of OAT is the causative biochemical defect in GA and the first to report causative mutations in the OAT gene. He has personally overseen the metabolic management of more than 50 patients with GA.
Dr. Singh is an Assistant Professor of Ophthalmology and Genetics. He trained in medicine in Singapore, completed a PhD at the University of Oxford (U.K.) as a Merton College Graduate Prize Scholar, followed by clinical and surgical retina fellowships at Oxford Eye Hospital and Moorfields Eye Hospital in the U.K. He is a practicing retinal specialist and vitreoretinal surgeon at the Wilmer Eye Institute, Johns Hopkins Hospital. He directs the adult inherited retinal disease service and visual electrophysiology diagnostic laboratory at Wilmer. He co-directs the Wilmer Genetic Eye Disease Center (GEDI) with Dr. Doyle and is a faculty member of the Stem Cell and Ocular Regenerative Medicine (STORM) Center. His laboratory research centers on retinal regenerative medicine, with a focus on cell and gene therapy including photoreceptor regeneration and host tissue responses. He has developed novel gene and cell therapy surgical delivery approaches that are safe for children. He is study Chair of the multicenter Gyrate Atrophy Ocular and Systemic (GYROS) study, working closely with Co-Chair Dr. David Valle. He leads several clinical trials and studies on inherited retinal diseases at Johns Hopkins and is a Hartwell Investigator.
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