For children and adults in the study, functional improvements in vision followed single injections of genes that produced proteins to make light receptors work in their retinas.
The 12 subjects ranged in age from 8 to 44 years old at the time of treatment. Four of the children, aged 8 to 11, are the world's youngest individuals to receive gene therapy for a non-lethal disease (A fifth subject was 17 years old). On the other end of the age scale, the 35-year-old man and 44-year-old woman are the oldest patients to ever receive gene therapy for retinal degeneration.
For the current human trial, the research team used a vector, a genetically engineered adeno-associated virus, to carry a normal version of the gene, called RPE65, that is mutated in one form of LCA, called LCA2, that accounts for 8 to 16 percent of all LCA cases. Jeannette Bennicelli, Ph.D., in Bennett's laboratory, cloned the gene. The clinical vector production facility at Children's Hospital's Center for Cellular and Molecular Therapeutics (CCMT), directed by Fraser Wright, Ph.D., manufactured the vector.
The clinical trial brought together subjects and scientists from two continents. Five patients enrolled in the study were identified at the Department of Ophthalmology at the Second University of Naples, an institution with a long-standing program in researching inherited retinal diseases, under the supervision of Francesca Simonelli, M.D. Two children from Belgium were recruited through Ghent University Hospital, under the supervision of Bart Leroy, M.D., Ph.D. Jennifer Wellman, of the CCMT, directed all local and federal regulatory interactions for the study.
Another co-author, Edwin Stone, M.D., Ph.D., Howard Hughes Medical Institute Investigator and director of the Carver Center, a genetic testing laboratory at the University of Iowa, identified and verified several of th
|Contact: Karen Kreeger|
University of Pennsylvania School of Medicine