Summary: 
The National Eye Institute seeks research co-development partners and/or licensees for a therapy using an FDA-approved small molecule drug reserpine (and related compounds especially halofantrine) that prevents photoreceptor cell death in retinal degenerations.

Description of Technology: 
Inherited Retinal Degenerations (IRD), such as Leber Congenital Amaurosis (LCA) and retinitis pigmentosa (RP), are characterized by a progressive loss of photo-sensitive cells in the retina. Most forms of IRD have no therapeutic options available due to their genetic heterogeneity and/or lack of mechanistic understanding. In particular, LCA represents roughly 5% of all retinal dystrophies and results in severe vision loss at an early age. There is an FDA-approved treatment for one form of LCA caused by mutations in the RPE 65 gene. This involves injection of an adenovirus vector containing the normal copy of the RPE65 gene. Long-term data for the gene therapy achieved only transient results: progressive reduction in visual acuity, sensitivity and function occurred following an initial gain seen 6-12 months post-treatment. 

RP is a collection of rare eye diseases that affect roughly 1 in 4000 people worldwide. Currently, as there are no treatments, a majority of affected individuals lose most of their sight.

By 2040, age-related macular degeneration (AMD) will affect ~288 million people worldwide. AMD is the leading cause of blindness in all developed countries. Identifying eyes at high risk of progression to late AMD, the stage associated with blindness, is vital. This would allow timely medical treatments, lifestyle interventions, more tailored home monitoring and improved clinical trials for patients.

Scientists at the National Eye Institute (NEI) have developed a mutation-independent method to treat LCA, RP, other IRDs, and AMD using the FDA-approved small molecule, Halofantrine (NCGC00016833-01). Halofantrine, which was previously approved to treat malaria, helped protect photoreceptors from cell death in three different IRD model systems in 1) retinal organoid model systems, 2) two different mouse models, and 3) rat models. Furthermore, packaging Halofantrine and other potential candidate compounds for conjunctival delivery into the eye via eye drops is under development. 

These small molecules act by targeting several cellular pathways which are also affected in diseases of other organs, suggesting that they may be useful in treating other, mutation independent ocular diseases.

Potential Commercial Applications: 

• Therapeutic to treat Leber congenital amaurosis
• Therapeutic to treat Inherited Retinal Disorders associated with photoreceptor degeneration
• Therapeutic to treat AMD
• Therapeutic to treat mutation-independent ocular diseases

Competitive Advantages:

• Less time-consuming, costly and labor intensive versus the development of individualized gene therapies
• Small molecules are scalable with cost-effective manufacturing
• Small molecules are highly penetrant with easy routes of administration
• Small molecules can be delivered via eye drops or as intra-vitreal injection
• Less intrusive and easy administration route
• Conjunctival delivery and eye drop formulation more accessible than retinal implant or injection