Gene therapy for childhood blindness

Genzyme has announced the establishment of a research collaboration with the University of Florida (UF) and the University of Pennsylvania to develop gene therapy for the treatment for Leber congenital amaurosis type 1 (LCA-1), which is usually diagnosed in children who are less than a year old, and patients remain severely visually impaired for the rest of their lives. This disease, which is the most common cause of childhood blindness, is a group of degenerative diseases of the retina caused by genetic mutations in one of 19 genes currently associated with the disorder. These genes encode proteins that play a variety of roles in the development and function of the retina, and a mutation in any one of them can cause visual impairment.

from nature.com

Genzyme is providing $900,000 in funding over three years to Dr. Shannon Boye, assistant professor of ophthalmology at the University of Florida, to fund her LCA-1 research. Dr. Boye’s research is focused on a gene called guanylate cyclase 1 (GUCY2D) that is mutated in LCA-1 patients. The GUCY2D gene normally makes GC1, a protein expressed in photoreceptors, which are located in the retina and convert light into electrical signals that the brain interprets as vision. Dr. Boye’s research shows that replacement of the gene using a viral vector restores function to the retina and results in long term useful vision in an otherwise blind mouse.

According to the National Institutes of Health, of the 3,000 people in the U.S. who have Leber congenital amaurosis, approximately 15 percent carry mutations in GUCY2D, making this a leading form of the disease.

Work is now underway to carry out pre-clinical studies required for FDA approval to test this therapy in Phase I clinical trials. The method will involve supplying patients with a normal, healthy, non-mutated copy of the GUCY2D gene. The researchers will accomplish this by taking a naturally occurring virus, adeno-associated virus, removing its viral DNA and replacing it with a normal copy of GUCY2D. An injection of these viral particles into the retina will then deliver GUCY2D to photoreceptors and potentially restore their function with a single treatment.

Studies are currently underway, during which Dr. Boye’s team will perform experiments designed to achieve FDA approval for using this form of gene therapy in patients. Specifically, they will focus on identifying the most effective adeno-associated virus and dose for safely delivering GUCY2D. 

Dr. Boye initially began work on the GUCY2D mutation a decade ago as a graduate student at UF. She and her colleagues have demonstrated that gene replacement can restore vision in four different animal models of this disease.

Prior research by colleagues at the University of Pennsylvania suggests that even older individuals with the GUCY2D mutation may be good candidates for this therapy, as patients with this disease tend to retain normal photoreceptor structure across a wide expanse of their retinas.

Genzyme’s funding supplements current funding from the Foundation Fighting Blindness.

The majority of the early stage LCA-1 research is being conducted at the University of Florida, with Genzyme taking on increasingly more activities as the program advances toward clinical trials. Genzyme has the option to in-license the potential treatment before it enters clinical trials.

Treating physicians of LCA-1 patients from the University of Pennsylvania are also playing a key role in this research. They will provide information to the University of Florida and Genzyme about indicators to look for in trials to know whether or not the therapy is working. They are also conducting a natural history study, which tracks how the retina of an LCA-1 patient progresses over time if untreated.

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