Richard L. Hurwitz, M.D.
Departments of Pediatrics, Ophthalmology, Molecular and Cellular Biology, and Center for Cell and Gene Therapy
M.D.: Albany Medical College, Albany
Postdoctoral training: University of Minnesota, Minneapolis
University of Washington, Seattle
Gene therapy, Adenoviral Transduction, Stem Cell, Retinoblastoma, Retinal Degenerative Diseases, Stargardt’s Disease
The Hurwitz laboratory studies the potential use of gene therapy for the treatment of ocular disease. Retinoblastoma is the most common malignant intraocular tumor of children and is caused by mutations in the retinoblastoma gene. Both transgenic and xenograft models of retinoblastoma have been established and are being used to study the cell of origin of the disease, to discern modes of metastatic behavior, and as models to develop new therapeutic strategies. Suicide gene transfer using an adenoviral vector to deliver the herpes thymidine kinase gene followed by treatment with ganciclovir has been shown to be successful in treating these animal models. A phase I clinical trial in children with retinoblastoma has shown that this modality is safe and may benefit children with vitreous tumor seeds, a complication for which there is no current therapy other than enucleation. A follow up protocol to further study this approach is in preparation. Metastatic retinoblastoma is usually fatal and no effective therapy is known, particularly for CNS disease. The potential use of an oncolytic virus to treat invasive and metastatic disease is being explored.
The human diseases that exhibit retinal degeneration are retinitis pigmentosa and macular degeneration. Mutations in the proteins that make up the phototransduction cascade as well as proteins that support the survival of photoreceptors have been found to result in retinal degeneration in animal models as well as to cause human disease. The Hurwitz group is studying the therapeutic delivery of photoreceptor proteins to diseased animals. The use of a viral vector to deliver the ABC4A transgene, a member of the ABCR transporter family and the vitamin A cycle mutations of which are the cause of juvenile onset macular degeneration is being explored. Viral vector delivery of the PDE6 transgene, a rod photoreceptor protein defective in retinitis pigmentosa, is also being explored. The ultimate goals of these studies are to examine the mechanisms of transduction and the toxicities of these agents and to evaluate different gene therapy techniques for the treatment of human ocular disease.
Adenoviral-based vectors that have been used to deliver potentially therapeutic genes to the ocular environment have been remarkably efficient. Studies recently published by the Hurwitz group suggest that adenoviral-mediated gene expression is modulated by hyaluronan and its CD44 receptor and additional studies to elucidate the mechanism of this regulation are ongoing. The ultimate goal of these studies is to be abe to modulate adenoviral vector mediated gene expression and treat human adenovirus infection, a major cause of illness.
Baylor College of Medicine
1102 Bates Street, Suite C1025.21
Houston, TX 77030
- Chaudhuri SR, Mallam JN, Chévez-Barrios P, Wadhwa L, Ng P, Hurwitz MY, Hurwitz, RL. (2007). Modulation of Adenoviral Transduction In Vitro and In Vivo by Hyaluronan and its Receptor CD44. Molecular Therapy 15: 566-570.
- Wadhwa, L, Hurwitz MY, Chévez-Barrios P, and Hurwitz RL. (2007). Treatment of invasive retinoblastoma in a murine model using an oncolytic picornavirus. Cancer Research. 67:10653-10656.
- Chintagumpala M, Chévez-Barrios P, Paysse EA, Plon SE, Hurwitz RL. (2007). Retinoblastoma: Review of current management. The Oncologist 12:1237-1246.
- Chong E-M, Coffee RE, Chintagumpala M, Hurwitz RL, Hurwitz MY and Chévez-Barrios P. (2006). Extensively necrotic retinoblastoma is associated with high risk prognostic factors. Arch. Path. Lab. Med. 130:1669-1672.
- Hurwitz RL, Shields CL, Shields JA, Chévez-Barrios P, Hurwitz MY and Chintagumpala MM. (2006). Retinoblastoma. In: Principles and Practice of Pediatric Oncology, 5th edition (Pizzo PA, Poplack DG, eds) Philadelphia, PA Lippincott-Williams & Wilkins, pp 865-886.
- Chévez-Barrios P, Chintagumpala M, Mieler W, Paysse E, Boniuk M, Kozinetz C, Hurwitz MY and Hurwitz RL. (2005). Response of retinoblastoma with vitreous tumor seeding to adenovirus-mediated delivery of thymidine kinase followed by ganciclovir. J. Clin. Oncol. 23:7929-7935.
- Mallam J, Hurwitz MY, Mahoney T, Chévez-Barrios P and Hurwitz RL. (2004). Efficient gene transfer into retinal cells using adenoviral vectors: Dependence on receptor expression. Invest. Ophthalmol. Vis. Sci. 45:1680-1687.
- Suber ML, Hurwitz MY, Chévez-Barrios P and Hurwitz RL. (2001). Immune consequences of intraocular administration of modified adenoviral vectors. Human Gene Therapy 12:833-838.
- Chévez-Barrios P, Hurwitz MY, Louie K, Marcus KT, Holcombe VN, Schafer P, Aguilar-Cordova E and Hurwitz RL. (2000). Metastatic and non-metastatic models of retinoblastoma. Am. J. Path. 157:1405-1412.
- Hurwitz MY, Marcus KT, Chévez-Barrios P, Louie K, Aguilar-Cordova CE and Hurwitz RL. (1999). Suicide gene therapy for treatment of retinoblastoma in a murine model. Human Gene Therapy 10:441-448.