Sorbitol dehydrogenase deficiency (SORD Deficiency) is a progressive, debilitating hereditary neuropathy that affects peripheral nerves and motor neurons, resulting in significant disability, loss of sensory function and decreased mobility. Recently, mutations in the SORD gene resulting in loss of the enzyme sorbitol dehydrogenase (SORD) function, and consequent intracellular sorbitol accumulation, were shown to be responsible for disease in a subset of patients previously diagnosed with Charcot-Marie-Tooth disease (CMT2) or distal hereditary motor neuropathy (dHMN). These patients can now be more accurately diagnosed with SORD Deficiency.
SORD Deficiency impacts an estimated 1 in 100,000 individuals. In the U.S., there are about ~3,300 individuals with mutations in the SORD gene (~7-9% CMT2/dHMN patients). SORD’s role in metabolism is well defined, and an understanding of this genetic and biochemical basis of disease offers new opportunities for treatment of patients with neuropathy caused by SORD deficiency. There are currently no approved drugs for patients with SORD Deficiency.
Applied Therapeutics is committed to advancing research into the causes of and treatment for SORD Deficiency.
In SORD Deficiency, the Aldose Reductase enzyme converts glucose to sorbitol, which then builds up in tissues causing symptoms of neuropathy. Our AT-007 program focuses on the targeted inhibition (or “turning off”) of Aldose Reductase. AT-007 is Applied Therapeutics’ lead investigational treatment, which could change the lives of people living with SORD Deficiency, as well as other diseases caused by Aldose Reductase.
AT-007 has the potential to be the first FDA-approved therapy for SORD Deficiency.