The long-term goal of this work is to develop an oral drug for the prevention of age-related macular degeneration (AMD). AMD is the leading cause of blindness in the United States, with 8 million Americans diagnosed or at risk of irreversibly losing vision, and over 2 million people who already have debilitating vision loss. Currently, there is no FDA-approved preventative treatment for AMD. One of the earliest changes in the retina that precede symptoms of AMD is the formation of toxic vitamin A dimers. ALK-001 is a chemically-modified vitamin A, in which 3 hydrogen atoms have been replaced by 3 deuterium atoms at carbon number 20. Replacing the retina's vitamin A with ALK-001 slows the formation of toxic vitamin A dimers. To date, ALK-001 is the only small molecule designed to prevent the dimerization of vitamin A that has demonstrated functional preservation of visual function in animal models. The central hypothesis of this work is that retarding vitamin A dimerization will slow the development and/or progression of AMD. The specific objective of this application is to further develop ALK-001 and generate clinical data so that phase 3 or 4 confirmatory clinical trials can be designed to assess the extent to which inhibiting the dimerization of vitamin A slows the development and/or progression of AMD. We plan to achieve this goal by completing the following specific aims:
AIM 1 : Determine the feasibility of manufacturing ALK-001 on a commercial scale. This will be achieved by assessing the limitations of our current synthetic route to determine if it can be used to manufacture ALK- 001 on a commercial scale.
AIM 2 : Evaluate the effect size of ALK-001 on the progression of geographic atrophy (GA) due to AMD. This will be achieved by performing an 18-month double-masked, placebo-controlled study in 80 subjects with geographic atrophy. An oral drug to prevent the development and/or worsening of AMD would have a tremendous impact on the quality of life of millions of Americans. The dimerization of vitamin A has long been hypothesized to be a major contributor of the development of AMD. However, we lack clinically-amiable strategies to safely prevent its dimerization. This limits our ability to determine the extent to which dimerization participates in the progression of AMD. ALK-001 is a new compound that has been shown to prevent the dimerization of vitamin A without negatively affecting the visual cycle or depriving the photoreceptors of vitamin A, and thus could possibly slow the progression of AMD.

Public Health Relevance

The proposed research is relevant to overall public health because it seeks to evaluate the safety and efficacy of ALK-001, a potential treatment for age-related macular degeneration (AMD), the leading cause of blindness in the United States. The prevalence of intermediate and advanced AMD increases steadily with age (7% of the 65-69 year old group, 24% of the 80+ year old group). As the number of elderly is also increasing, the number of people at risk of AMD will increase in 2025 by close to 50% from today's numbers. Despite constantly improving treatments for wet-AMD, also known as choroidal neovascularization (CNV), over 80% of patients have the dry form of AMD and remain without any approved treatment today. It is therefore imperative to develop safe and effective, prophylactic treatments to prevent the development of the disease. To date, direct costs of healthcare due to AMD are estimated to be over $100 billion per year (AMD Alliance Report). As such, a treatment that could slow, stop or prevent AMD could have significant public health impact, and is also relevant to the NIH's mission of developing fundamental and clinical knowledge to help and reduce the burdens of human disability.

National Institute of Health (NIH)
National Eye Institute (NEI)
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Wujek, Jerome R
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Alkeus Pharmaceuticals, Inc.
United States
Zip Code