In this webinar, Dr. Shoshana Shendelman, Founder and CEO of Applied Therapeutics, shares a clinical trial update on SORD Deficiency, one of the most common genetic causes of Charcot-Marie-Tooth type 2 (CMT2) and distal hereditary motor neuropathy (dHMN). This is Part 2 of HNF’s SORD webinar series, focused on the investigational treatment in development and the research underway to bring it to patients.

What is SORD Deficiency?

Sorbitol Dehydrogenase (SORD) Deficiency is a recently discovered, rare genetic metabolic condition. People with SORD Deficiency are missing a key enzyme needed to break down a sugar called sorbitol, which then builds up to toxic levels and damages the peripheral nerves. Before the SORD gene was identified in 2020, many of these patients were diagnosed by their symptoms alone, as CMT2 or dHMN. We now know that up to roughly 1 in 10 cases in those categories may be SORD related, with an estimated 3,300 people in the United States carrying the gene variant. Symptoms usually begin around age 17 on average, though they can appear in early childhood or as late as a person’s forties, and typically include muscle weakness and wasting in the legs and arms.

The clinical trial in this update

At the time this webinar was recorded, Applied Therapeutics, an HNF TRIAD research partner, was conducting an international Phase 3 study called INSPIRE. INSPIRE is a double-blind, placebo-controlled trial of once-daily oral govorestat (AT-007), a therapy designed to lower the toxic sorbitol that drives nerve damage in SORD Deficiency. Dr. Shendelman’s update walks through how the treatment is intended to work, the goals of the trial, and what taking part in a SORD study involves.

Where things stand now

A great deal has happened since this webinar was recorded in 2022. The INSPIRE trial has since reported positive results, and govorestat has been advancing toward FDA review. For the latest:

Could this affect you?

If you have been diagnosed with CMT2 or dHMN, genetic testing can show whether SORD Deficiency is the underlying cause, and that answer can open the door to research and, potentially, treatment. Learn more about CMT-SORD, and consider joining the Global Registry for Inherited Neuropathies (GRIN) so the community can be matched with research opportunities as they open.

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