Sjögren-Larsson Syndrome (SLS) is a rare genetic disease caused by mutations in an enzyme that metabolizes fatty (long-chain carbon) RASP, resulting in itchy skin, and severe neurological and retinal disorders. Genetic mutation analysis suggests that there are approximately 1,300 SLS patients in the United States and a greater number of SLS patients in Europe.
Reproxalap, Aldeyra’s lead reactive aldehyde species (RASP) inhibitor, is being developed in SLS for the treatment of ichthyosis, a serious skin disorder characterized by excessive dryness, leading to compromise of dermal integrity, infection, and bleeding. Other RASP inhibitors in Aldeyra’s pipeline may be tested in SLS retinal or neurological diseases.
The ichthyosis in SLS is usually present at birth and stabilizes within the first two years of life, affecting most of the body except the face, palms, and soles. SLS patients are often unable to care for themselves, and require constant monitoring, intensive daily patient care that includes extended bathing routines over multiple hours, and frequent doctor visits. The time required to attend to SLS patients often prevents caregivers from working outside the home.
In addition, considerable social stigma and emotional burden is common, especially given scale odor, the flaking skin, and the external misperception that SLS patients suffer from diffuse cutaneous infectious disease. There is currently no therapy approved for the treatment of SLS, though some patients and their caregivers apply non-specific topical creams, including keratinolytics (acids that soften skin), moisturizers, and retinoids.
The ichthyosis in SLS is thought to be caused by RASP-mediated modification of lipids (fats) that are generated in the epidermis (the most superficial layer of skin) to form a moisture barrier that holds water in the skin. Moisture barrier compromise leads to water loss, which in turn leads to the epidermal dryness and thickening that are characteristic of ichthyosis. We believe that by lowering levels of RASP and thereby preventing lipid modification and the ensuing moisture barrier dysfunction, our lead RASP inhibitor reproxalap, when applied topically to the skin, has the potential to ameliorate the dermatologic symptoms of SLS.
In April 2017, reproxalap received orphan drug designation from the FDA for the treatment of congenital ichthyosis, including the ichthyosis characteristic of SLS.