Living with Sjogren Larsson Syndrome
Sjögren-Larsson Syndrome (SLS):
An aldehyde-mediated orphan disease with no approved therapy.
Sjögren-Larsson Syndrome (SLS) is caused by genetic mutations in Fatty Aldehyde Dehydrogenase (FALDH), an enzyme that metabolizes long-chain aldehydes. These mutations result in high levels of free aldehydes, leading to the accumulation of fatty aldehydes or precursor molecules that are generally 16 to 18 carbons in length. Aldehyde accumulation is believed to result in the pathology of SLS, which includes a severe skin disorder called ichthyosis, as well as mental delay, spasticity, and in some patients, retinal disorders.
The most prevalent complaint from patients and caregivers.
The primary day-to-day complaint of Sjögren-Larsson Syndrome patients and their caregivers is ichthyosis: severely dry, itchy skin.
Under normal circumstances, lipids (fats) are generated in the epidermis, the most superficial layer of skin, forming a natural moisture barrier that holds water in the skin. The dermatologic disease in SLS is thought to be caused by aldehyde-mediated compromise of the natural moisture barrier, resulting in water loss, which in turn leads to the scaly, itchy, thickened skin characteristic of ichthyosis.
Patients with this debilitating disease are consistently disturbed by their dermal symptoms, which affect most of the body surface, and often excoriate their skin by scratching.
The potential of ADX-102 for the treatment
of severe ichthyosis.
There is currently no FDA-approved therapy specifically for treating the severe ichthyosis associated with SLS.
Aldeyra’s lead compound, ADX-102, has the potential to ameliorate the dermatologic symptoms of SLS. By trapping fatty aldehydes when applied topically to the skin, ADX-102 could significantly lower aldehyde levels — thereby preventing the lipid modification and ensuing moisture barrier dysfunction that causes ichthyosis in SLS patients.
A tremendous unmet medical need.
Some patients and their caregivers apply non-specific topical creams including keratinolytics (acids that soften skin), moisturizers, and retinoids. At Aldeyra, we believe the effects of keratinolytic and moisturizing creams are minimal in treating severe ichthyosis and that retinoids are unsuitable for chronic use due to their toxicity.
How Sjögren-Larsson Syndrome begins:
And its prevalence worldwide.
While some patients are believed to inherit Sjögren-Larsson Syndrome, most occurrences of this worldwide disease appear to be due to sporadic mutations. Since the severe ichthyosis presents at birth, SLS patients born in the United States are generally diagnosed when they are neonates. The disease persists lifelong.
To our knowledge, Sweden is currently the only country to have estimated the prevalence of the Sjögren-Larsson Syndrome — at 1 per 250,000 people. Extrapolating from the Swedish estimate, it is generally assumed there are approximately 1,000 or fewer SLS patients in the United States, but a larger number in Europe.
In the third quarter of 2016, we announced positive data from our randomized, vehicle-controlled, double-masked clinical trial of topical dermatologic ADX-102 to treat the skin disease in patients with SLS. The skin of all ADX-102-treated patients improved, and the magnitude of improvement was statistically greater than that of vehicle-treated patients. The results of the clinical trial suggest that ADX-102 could be the first mechanistically directed therapy in SLS.
The Foundation for Ichthyosis & Related Skin Types, Inc.® (FIRST) is the world's leading patient advocacy organization dedicated to improving lives and seeking cures for those affected with ichthyosis or a related skin type. FIRST educates, inspires and connects all affected individuals, their families, medical professionals and the general public with regard to these specific sets of skin disorders. FIRST is also the only patient advocacy organization funding research in the field of treatments and cures for ichthyosis.