The Ocular Gene Therapy Research Laboratory of Richard Hurwitz, MD

The Hurwitz laboratory studies the use of gene therapy in the treatment of ocular disease. Retinoblastoma is the most common malignant intraocular tumor of children and is caused by mutations in the retinoblastoma gene. Using a mouse model of this disease, they have shown that suicide gene therapy using an adenoviral vector to deliver the herpes thymidine kinase gene followed by treatment with ganciclovir can shrink the tumor. Based on these studies, an FDA- and RAC-approved clinical trial has been opened to investigate the use of this therapy for children with retinoblastoma. The Hurwitz laboratory is also studying the use of gene replacement therapy using the normal retinoblastoma gene delivered by an adenoviral vector for the treatment of this disease. Retinoblastoma has a unique mode of metastasis. In vitro and in vivo models of metastatic retinoblastoma that closely mimic human disease have been developed. Using these models, they are studying the role of metalloproteinases in the early stages of retinoblastoma metastasis. Their goal is to use this knowledge to find a successful treatment to prevent and treat this devastating complication of retinoblastoma.

Dr. Hurwitz is also exploring the use of gene therapy as a treatment for retinal degenerative diseases such as retinitis pigmentosa and macular degeneration. An adenoviral vector has been designed to deliver a normal ABCA4 gene that encodes a protein responsible for retinal recycling. The ABCA4 gene is defective in juvenile macular degeneration (Stargardt’s Disease) and in some forms of autosomal recessive retinitis pigmentosa. The ultimate goals of these studies are to examine the toxicities of these agents and to explore the use of different gene therapy techniques for the treatment of malignant and non-malignant human ocular disease.

The use of adenoviral vectors in the ocular environment has been remarkably successful. The Hurwitz laboratory has found that hyaluronic acid, a prominent component of the vitreous, can enhance adenoviral transduction efficiency up to 1.5 orders of magnitude in part through its interaction with the hyaluronic acid receptor, CD44. In addition, enzymatic degradation of hyaluronic acid may prevent adenoviral transduction. The laboratory is currently exploring the potential for use of hyaluronic acid as a mediator of adenoviral infection in the clinical setting.