Randomized trial of l-serine in patients with hereditary sensory and autonomic neuropathy type 1

OBJECTIVE: To evaluate the safety and efficacy of l-serine in humans with hereditary sensory autonomic neuropathy type I (HSAN1). METHODS: In this randomized, placebo-controlled, parallel-group trial with open-label extension, patients aged 18–70 years with symptomatic HSAN1 were randomized to l-serine (400 mg/kg/day) or placebo for 1 year. All participants received l-serine during the second year. The primary outcome measure was the Charcot-Marie-Tooth Neuropathy Score version 2 (CMTNS). Secondary outcomes included plasma sphingolipid levels, epidermal nerve fiber density, electrophysiologic measurements, patient-reported measures, and adverse events. RESULTS: Between August 2013 and April 2014, we enrolled and randomized 18 participants, 16 of whom completed the study. After 1 year, the l-serine group experienced improvement in CMTNS relative to the placebo group (−1.5 units, 95% CI −2.8 to −0.1, p = 0.03), with evidence of continued improvement in the second year of treatment (−0.77, 95% CI −1.67 to 0.13, p = 0.09). Concomitantly, deoxysphinganine levels dropped in l-serine-treated but not placebo-treated participants (59% decrease vs 11% increase; p < 0.001). There were no serious adverse effects related to l-serine. CONCLUSION: High-dose oral l-serine supplementation appears safe in patients with HSAN1 and is potentially effective at slowing disease progression. CLINICALTRIALS.GOV IDENTIFIER: NCT01733407. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that high-dose oral l-serine supplementation significantly slows disease progression in patients with HSAN1.