Stargardt disease is a rare yet life devastating condition. It is the most common form of inherited macular degeneration, and affects about one in 10,000 people (about 30,000 people in the United States). There is currently no cure or treatment for Stargardt disease but clinical trials using gene and cell therapies are currently undergoing. Patients with Stargardt most often start experiencing significant vision loss during their childhood and teenage years (60% of the patients are diagnosed before 20 years of age). This vision loss cannot be corrected by glasses, and diagnosis had been traditionally delayed due to the young age of the patients and the rareness of the disease. After diagnosis, and depending on age at onset, vision deteriorates progressively to levels below 20/200 (legal blindness). The disease affects mostly the central vision and spares some of the peripheral vision, although there are very severe forms that lead to complete blindness. Almost all of those affected by Stargardt disease will live legally blind during their adult lives, although patients with late onset may retain some visual acuity. Loss of central vision leads to impossibility to perform tasks such as reading, writing, driving or recognizing faces.
In 1997, scientists discovered that Stargardt disease results from a defective gene, the ABCA4, responsible for the synthesis of an important protein called Rim protein. A normally functioning Rim protein transports vitamin A molecules from the photoreceptors (the molecules sensitive to light) back into specialized cells (called RPE), where vitamin A molecules are recycled to be reused for vision. In Stargardt, the defects in the ABCA4 gene lead to partial or full dysfunction of this protein. As a result, vitamin A transport is affected and vitamin A molecules tend to accumulate in the photoreceptors. This accumulation leads to the formation of toxic pigments (known as "vitamin A dimers") believed to be partly responsible for vision loss. Although normal individual also form vitamin A dimers, this process usually takes decades, explaining why age-related macular degeneration (AMD) occurs later in life of normal people, while the same process takes only a few years in Stargardt explaining vision loss from childhood.
If the involvement of vitamin A dimers in Stargardt is now relatively well accepted and if genetic tests can now accurately diagnose the disease, there has been unfortunately little attention paid to Stargardt compared to the more prevalent AMD. An explanation could be that Stargardt is a very rare disease with few patients compared to other diseases, making it less attractive for pharmaceutical companies to develop a treatment for this disease. Rare diseases are therefore called "orphan diseases" due to this lack of interest from drug developers.
Alkeus Pharmaceuticals is committed to searching and developing cures or treatments for serious ophthalmic conditions, and despite its rareness, a treatment for Stargardt disease would have a major impact on the lives of hundreds of thousands of people worldwide, particularly as patients with Stargardt lose vision from as early as 6 and would benefit the most from a treatment that could slow or stop the progression of vision loss. Such a treatment is generally called a "disease modifying drug", as it has the potential to alter the course of the disease and slow it down. It is unknown whether a disease modifying drug could also help restore some of the lost vision.
In addition, due to similarities between Stargardt and dry-AMD, a better understanding of Stargardt disease could undoubtedly contribute to better understanding of dry-AMD and perhaps help develop a novel treatment that could save millions of people with dry-AMD.
Alkeus' lead compound, ALK-001, is an oral compound with a well-understood mechanism of action. ALK-001 was specifically designed to treat Stargardt disease by preventing the formation of these toxic vitamin A dimers in the eye. ALK-001 has been cleared by the U.S. Food and Drug Administration (FDA) to start a clinical trial. Clinical trials are needed to assess the safety and effectiveness of a drug.
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