Molecular Targets for Modulating Intraocular Pressure and Differentiation of Steroid Responders versus Non-Responders
Stephen G. Schwartz and M. Elizabeth Fini
Problem
Corticosteroid therapy is a common treatment for various diseases of the eye such as exudative age-related macular degeneration, diabetic macular edema, retinal vein occlusion, and uveitis. A major complication of this treatment is an increase in intraocular pressure (IOP), which may be severe and intractable. This increase may lead to permanent optic neuropathy. The etiology of the steroid response has never been determined, although a possible genetic component has long been suspected. Presently, it is not possible to predict which patients will have this steroid response. Concerns about this side effect have probably limited the clinical use of this otherwise effective medication.
Solution
If it were possible to identify steroid responders prior to treatment, the use of steroids would become much safer, and potentially more common. Further, the ability to separate a patient population into responders and non-responders would be of great benefit to the design of clinical trials on corticosteroid drugs for use in the eye. There is an urgent need to develop a method that can predict whether a patient should or should not have corticosteroid therapy. The inventors have identified 48 single nucleotide polymorphisms which correlate, to a statistically significant degree, with the magnitude of IOP change following steroid therapy. If the relationship between these 48 polymorphisms and IOP response following steroid therapy is confirmed, this is the first method that will estimate the risk, prior to steroid therapy, of any individual patient developing increased IOP.
Competitive Advantage
This is the only method that has the capacity to predict what patients might suffer adverse reactions to corticosteroid therapy.
Applications
(1) This could be developed into a kit that would determine whether a patient has the polymorphisms that suggest IOP response following steroid therapy;
(2) Futhermore, these polymorphisms may provide potential molecular drug targets for the treatment of steroid-induced glaucoma;
(3) A better understanding of the pathogenesis of steroid-induced glaucoma would increase our understanding of the more common primary open-angle glaucoma, which is a leading worldwide cause of preventable blindness.
Patent Status
International Patent Application entitled
"MOLECULAR TARGETS FOR MODULATING INTRAOCULAR PRESSURE AND DIFFERENTIATION OF STEROID RESPONDERS VERSUS NON-RESPONDERS" filed on December 04, 2008.
Licensing Opportunity
We are seeking collaborative research and commercial options to further develop this technology.
About the Inventors
Stephen G. Schwartz, M.D., received his medical degree from New York University School of Medicine in 1995. He completed ophthalmology residency training at NYU in 1999 and fellowship training in vitreoretinal surgery at Baylor College of Medicine in 2001. He is currently pursuing an M.B.A. through Northwestern University's Kellogg School of Management. He served as assistant professor of ophthalmology and program director at Virginia Commonwealth University until 2004. He is currently assistant professor of clinical ophthalmology at the University of Miami Miller School of Medicine and medical director and division chief of the Bascom Palmer Eye Institute Retina Center at Naples. His major research interest is ophthalmic pharmacogenomics. In 2005, he demonstrated an association between single nucleotide polymorphisms in the 1-adrenergic receptor and clinical response to betaxolol. This was the first such pharmacogenomic publication in the ophthalmologic literature.
Selected References
Schwartz SG, Ayala-Haedo JA, Kishor KS, and Fini ME. Pharmacogenomics of open-angle glaucoma. Current Pharmacogenomics and Personalized Medicine, 2008, in press.
Schwartz SG, Puckett BJ, Allen RC, Castillo IG, and Leffler, CT. 1-adrenergic receptor polymoprhisms and clinical efficacy of betaxolol hydrochloride in normal volunteers. Ophthalmology, 2005;112:2131-2136.
