Stargardt Disease
Age-Related Macular Degeneration
We invented a new vitamin A that holds tremendous promise in preventing blindness for millions of people.
Vitamin A enables vision by capturing photons of light and sending the resulting signals to the brain.
But vitamin A is not ideal. It is unstable. It reacts with itself, dimerizes, forming harmful vitamin A dimers that damage cells. The eye has evolved adaptive mechanisms to mitigate the deleterious dimerization of vitamin A.
One such adaptation is a Rim protein, which promptly grabs the reactive form of vitamin A, before it dimerizes, and moves it to a safer place in the cell away from other vitamin A molecules.
In some individuals, genetic mutations in the ABCA4 gene cause the Rim protein to malfunction, leading to the accelerated dimerization of vitamin A—this condition, known as Stargardt disease, results in retinal degeneration. There is currently no treatment for Stargardt disease: individuals with Rim protein mutations are born with normal vision but gradually progress to legal blindness.
I invented a new vitamin A that dimerizes less readily than old vitamin A. This new vitamin A functions similarly to old vitamin A but demonstrates a reduced propensity to dimerization, in the presence of a malfunctioning Rim protein.
This new vitamin A is being tested as a treatment for Stargardt disease by Alkeus Pharmaceuticals.
"I think age-related macular degeneration (AMD) is caused by the accelerated dimerization of vitamin A, resulting from a dysfunctional Rim protein (ABCA4) due to age-related declines in ATP."
Interestingly, the Rim protein relies on adenosine triphosphate (ATP) as an energy source to transport vitamin A. As we age, the amount of ATP in the retina decreases by over 70%. I think the age-related decline in retinal ATP results in a dysfunctional Rim protein, which results in the accelerated dimerization of vitamin A, which drives the development of age-related macular degeneration (AMD).
About 2 million Americans have vision loss due to age-related macular degeneration. If the above theory is correct, the new vitamin A could also prevent and treat age-related macular degeneration.
Published May 25, 2023
This new Vitamin A called ALK-001 is being developed by Alkeus Pharmaceuticals
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LHON
Leber Hereditary Optic Neuropathy
In Leber hereditary optic neuropathy (LHON), faulty mitochondrial DNA causes decreased ATP and increased superoxide radical anions, leading to the degeneration of the optic nerve and profound vision loss.
We have developed a small molecule that corrects ATP and superoxide radical anions in the presence of the defective DNA.
This new molecule holds promise for thousands of individuals and caregivers living with LHON.