Wet Age-Related Macular Degeneration

Visit patient sites: Foundation Fighting Blindness, The Macula Vision Research Foundation, Retina International, Research to Prevent Blindness

Wet AMD is the leading cause of blindness in the US, with more than 1.6 million people affected. Each year approximately 200,000 new cases are diagnosed in the US and more than 500,000 worldwide.

The macula is the area of the retina with the highest density of cone photoreceptors and is therefore essential for fine-detail vision required for activities such as reading and driving. In patients with wet AMD, the macula is disrupted by fluid leaking from new blood vessels that have grown under the retina. This leads to loss of central vision which effectively blinds a patient for most normal activities.

A key signal of new vessel growth (neovascularization) is vascular endothelial growth factor (VEGF). VEGF also promotes leakiness of the new vessels. These twin effects have made VEGF a key target of AMD drug development efforts. Two recently developed compounds, pegabtanib (Macugen) and ranibizumab (Lucentis), which target VEGF and reduce neovascularization have been approved by the FDA for treatment of wet AMD. Effective treatment with each of these drugs requires frequent injections into the affected eye. This is not only inconvenient but is a significant hurdle for many patients.

AGTC, in collaboration with Genzyme Corp., is developing a gene therapy product that will provide long-term suppression of VEGF, thereby freeing patients and physicians from the need for frequent injections. The product will remain resident in the treated eye and the patients’ own cells will produce the VEGF blocking agent continuously and exactly where it is needed.

We have strong proof-of-concept data and have completed formal pre-clinical studies that will lead to initiation of clinical trials.

X-Linked Retinoschisis (visit patient site)

X-linked retinoschisis (XLRS) is an inherited form of retinal degeneration affecting young males. Patients present with poor vision either in infancy or at school age. Visual acuity usually worsens during the teenage years and then stabilizes until complicated by vitreous hemorrhage or retinal detachment during adulthood. There is no treatment available for the retinal degeneration in XLRS.

In animal models of XLRS, treatment with a gene therapy product leads to progressive and long-term improvement in retinal function and prevention of retinal cell degeneration. Based on the strong preclinical proof-of-concept data, AGTC has initiated a formal preclinical testing program that will lead to clinical evaluation of this product.

Achromatopisa (visit patient site)

Complete achromatopsia is an inherited condition that is associated with color blindness, visual acuity loss and extreme light sensitivity resulting in daytime blindness. There is no specific treatment for achromatopsia, although deep red tinted spectacles or contact lenses can reduce symptoms of light sensitivity.

In animal models of achromatopsia, treatment with a gene therapy product restored daylight visual function in affected dogs with daytime blindness. Based on the strong preclinical proof-of-concept data, AGTC has initiated a formal preclinical testing program that will lead to clinical evaluation of this product.

Glaucoma

Visit patient sites: Glaucoma Research Foundation , NEI/NIH, Research to Prevent Blindness

Glaucoma is a group of diseases of the optic nerve resulting in the death of retinal nerve cells. In the US, glaucoma is the second leading cause of blindness and the leading cause in African-Americans. Raised intraocular pressure is a significant risk factor for developing glaucoma, but there is no set threshold for intraocular pressure that causes glaucoma and in some patients glaucoma will develop despite normal intraocular pressure. Untreated glaucoma leads to permanent damage of the optic nerve and resultant visual field loss, which can progress to blindness.

The mainstay of glaucoma treatment is lowering intraocular pressure via drugs or surgery. The drugs used are usually delivered by eye drops, and adherence to medication protocols can be confusing and expensive. Poor compliance with medications and follow-up visits is a major reason for vision loss in glaucoma patients, and disease can progress despite normalization of intraocular pressure.

In animal models of glaucoma, treatment with a gene therapy product resulted in significant reduction in retinal nerve cell death. AGTC has initiated a preclinical testing program that will lead to clinical evaluation of this product.