L-Serine Study Results

A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, DELAYED-START TRIAL TO EVALUATE THE SAFETY AND EFFICACY OF L-SERINE IN SUBJECTS WITH HEREDITARY SENSORY AND AUTONOMIC NEUROPATHY TYPE 1 (HSAN1)

Vera Fridman1, Peter Novak2, William David3, Anne Louise Oaklander3, Eric Macklin3, Diane McKenna-Yasek2, Kailey Walsh3, Robert Brown2, Thorsten Hornemann4, Florian Eichler3  1University of Colorado Medical Center, Denver, US., 2University of Massachusetts Medical School, Worcester, US.,3 Massachusetts General Hospital (MGH), Boston, US., 4University Hospital Zurich, Clinical Chemistry, Zurich, Switzerland.

Introduction: Hereditary Sensory Autonomic Neuropathy Type 1 (HSAN1) is a severe, autosomal dominant, axonal neuropathy that manifests with marked, small fiber predominant sensory loss, variable degrees of limb weakness, and skin ulceration. HSAN1 is caused by mutations in the SPTLC1 and SPTLC2 genes, which encode two of the three subunits of the enzyme serine palmitoyltransferase (SPT). Mutations in SPT induce a permanent shift in the substrate preference from serine to alanine thereby forming a class of neurotoxic deoxysphingolipids (dSL). Supplementation with L-serine reduces dSL levels in transgenic HSAN1 mice and results in clinical improvement of neuropathy. We report a two-year, delayed-start, placebo-controlled clinical trial evaluating the safety and efficacy of oral L-serine (400 mg/kg/d) in human subjects with HSAN1.

Results: All but 2 subjects (both of whom

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2016 Progress Report

Progress report on the L-serine HSAN1 Trial

by Florian Eichler, M.D.  (with Kailey Joan Walsh)

There were 18 subjects enrolled in this two-year, double-blind, placebo-controlled trial studying the efficacy of L-serine in patients with HSAN1. The study was initially randomized to placebo versus study drug, and both the participants and the investigators were blinded as to who was on placebo and who was on the study drug. At week 48 all participants were switched over to L-serine, regardless of their randomization from the previous year.

At the last DSMB (Data and Safety Monitoring Board) meeting (May 18, 2015) it was recommended that an open-label extension be added to the protocol. This would allow the continued collection of outcomes data on the first 16 subjects from the time they complete the original study to the time that the last two subjects complete the study in February 2016. Upon the board’s suggestion and after further investigation, it was decided that an extension of one year would be added to the protocol. After the original 2-year period, subjects would be given the option of being re-consented for the open label extension. All consented subjects would then be treated with L-serine (400 mg/kg/d) for

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