ADX-629 Therapy for Sjogren-Larsson Syndrome

Summary

This research study will determine whether orally administered ADX-629 is safe and has biochemical efficacy in participants with Sjögren-Larsson syndrome (SLS), a rare inherited disorder of fatty aldehyde metabolism The disease is caused by bi-allelic mutations in ALDH3A2, which results in deficient activity of fatty aldehyde dehydrogenase (FALDH) and leads to the build-up of harmful long-chain (C16-C20) aldehydes and alcohols. Accumulation of these lipids and their metabolic products in skin, brain and eyes is responsible for the symptoms, which persist lifelong. ADX-629 is an aldehyde trapping agent that is expected to eliminate fatty aldehydes and negate aldehyde toxicity, improve the biochemical abnormalities and have clinical efficacy for SLS. The primary objective of this clinical protocol is to determine whether ADX-629 is safe and tolerable for use in SLS subjects. The secondary objective is to determine the efficacy of ADX-629 in reversing the biochemical abnormalities in SLS. Exploratory objectives are to evaluate the short-term clinical effects of ADX-629 on neurologic, cutaneous and ophthalmologic disease in SLS. Participants will be treated with ADX-629 for 12 weeks and monitored for safety and biochemical efficacy.

Timeline

Start

2023-01-02

Primary completion

2026-04-01

Completion

2026-04-01

Publications

• Background Rizzo WB. Sjogren-Larsson syndrome: molecular genetics and biochemical pathogenesis of fatty aldehyde dehydrogenase deficiency. Mol Genet Metab. 2007 Jan;90(1):1-9. doi: 10.1016/j.ymgme.2006.08.006. Epub 2006 Sep 22.
• Background Rizzo WB. Genetics and prospective therapeutic targets for Sjogren-Larsson Syndrome. Expert Opin Orphan Drugs. 2016 Apr;4(4):395-406. doi: 10.1517/21678707.2016.1154453. Epub 2016 Mar 10.
• Background Rizzo WB, S'aulis D, Dorwart E, Bailey Z. Sjogren-Larsson syndrome: A biochemical rationale for using aldehyde-reactive therapeutic agents. Mol Genet Metab Rep. 2021 Dec 23;30:100839. doi: 10.1016/j.ymgmr.2021.100839. eCollection 2022 Mar.

Drugs

Indications