The Ocular Gene Therapy Research Laboratory of Dr. Richard Hurwitz and Dr. Mary Hurwitz
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.
The Hurwitz’s are 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.
Joshua Mallam, PhD
Joshua received his B.S. degree at Bayero Univesity-Bano in Nigeria, and obtained both his M.S. in virology and Ph.D. in molecular virology at Wuhan University in China. The focus of his thesis work was the selective replication by mutant adnovirus (AD5) in p53-deficient human tumor cells and tumor bearing mice using the GFP as a reporter gene. At Baylor, he has concentrated on creating and charaterizing chimeric adnoviral vectors that express either reporter proteins or potentially therapeutic gene products ABCA4. Since many ocular disorders are potential targets for gene therapy occur as a result of mutations in genes affecting photoreceptor function and viability, he is developing ways to specifically target these cells.
Vien studied at the Pharmacy University in Saigon, Viet Nam. She joined the lab in 1986 as the primary research assistant. She assists in numerous research projects including assaying and classifying phosphodiesterases isolated from retinoblastomas and measuring transmembrane bound proteases in an in vitro model of metatstatic retinoblastoma.
Patricia (Joy) Akinfewa
Laboratory Contact Information
Ocular Gene Therapy Research Laboratory
Drs. Mary Hurwitz and Richard Hurwitz
1102 Bates Street, Suite 1570
Houston, TX 77030