The objective of this proposal is to examine the efficacy of a novel adeno-associated virus (AAV) variant, ShH10, expressing neurotrophic factors for the treatment of glaucoma. Glaucoma is the second leading cause of blindness with high associated societal costs, and is expected to grow. The hallmark of glaucoma is retinal ganglion cell (RGC) death, which leads to optic nerve degeneration and vision loss. Current treatment strategies are limited to pharmacotherapy and surgery to lower intraocular pressure;many patients progress, however, despite adequately controlled pressure. Therefore new treatment strategies are needed for glaucoma, including those that target RGC survival. Although neurotrophic factors, including BDNF, NT4, and GDNF, have shown promise for glaucoma, they are rapidly cleared from the eye, and frequent intraocular injections are not practical for this chronic, slow- progressing disease. Recently, a variant of adeno-associated virus, called ShH10, has shown promise for the long-term delivery of neurotrophic factors to the retina. In this Phase I proposal, we plan to characterize the value of ShH10 for delivery of neurotrophic factors in two animal models of glaucoma, and identify the most promising neurotrophic factor for future development. If this Phase I project demonstrates efficacy of ShH10- mediated neurotrophic factor delivery, these experiments will lay the groundwork for Phase II studies to further substantiate the promise of this approach, including large-animal efficacy and toxicology studies, as a treatment for glaucoma.

Public Health Relevance

Glaucoma is the second leading cause of blindness worldwide, affecting over 2.2 million Americans and costing over $1.5 billion annually. Current strategies are limited to pressure-lowering eyedrops and surgeries, but despite adequately controlled pressure, many patients suffer poor outcomes. We propose to develop a new therapy that targets the survival of retinal neurons to improve the health outcomes for patients suffering from glaucoma.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Small Business Technology Transfer (STTR) Grants - Phase I (R41)
Project #
3R41EY022848-01S1
Application #
8627280
Study Section
Special Emphasis Panel (ZRG1-ETTN-G (12))
Program Officer
Wujek, Jerome R
Project Start
2012-09-30
Project End
2014-02-28
Budget Start
2012-09-30
Budget End
2014-02-28
Support Year
1
Fiscal Year
2013
Total Cost
$248,555
Indirect Cost
Name
Avalanche Biotechnologies, Inc.
Department
Type
DUNS #
016412260
City
Redwood City
State
CA
Country
United States
Zip Code
94061
Kim, Charles; Demetriades, Anna M; Radcliffe, Nathan M (2014) One Year of Glaucoma Research in Review: 2012 to 2013. Asia Pac J Ophthalmol (Phila) 3:48-55