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

Abstract

ObjectiveTo evaluate the safety and efficacy of l-serine in humans with hereditary sensory autonomic neuropathy type I (HSAN1).MethodsIn 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.ResultsBetween 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.ConclusionHigh-dose oral l-serine supplementation appears safe in patients with HSAN1 and is potentially effective at slowing disease progression.Clinicaltrials.gov identifierNCT01733407.Classification of evidenceThis study provides Class I evidence that high-dose oral l-serine supplementation significantly slows disease progression in patients with HSAN1.

Development of MRC Centre MRI calf muscle fat fraction protocol as a sensitive outcome measure in Hereditary Sensory Neuropathy Type 1

“…Comparable changes over 1 year were noted in NCS and SF36v2 between this study and the placebo group of the randomised trial. 7 Greater within-group variability was seen for IENFD (thigh) in the trial. This could reflect differences in techniques used for analysis.…”

“…A recent randomised, placebo-controlled trial in patients with HSN using oral L-serine supplementation by Fridman et al 7 did not show a significant difference in the primary outcome (proportion of patients progressing more than one point on the CMTNS at 1 year) between L-serine and placebo groups. However, it showed a decline in CMTNS (−1.5 units, 95% CI −2.8 to 0.1, p=0.03) in L-serine participants relative to placebo whereas the placebo group experienced a mean increase in CMTNS of 1.1 point (±0.53, p=0.04).…”

“…A small (18 patients) randomised placebo-controlled trial in HSN1 which has just been published has shown that oral L-serine treatment potentially slows disease progression. 7 A larger definitive efficacy trial of serine in the HSN1 population is warranted, however the major barrier is the lack of natural history data and responsive outcome measures.…”

Expanding the spectrum of SPTLC1‐related disorders beyond hereditary sensory and autonomic neuropathies: A novel case of the distinct “S331 syndrome”

“…However, we here provide some additional features, such as the relative preservation of distal sensory function, and consequent absence of foot ulcerations. Since oral l ‐serine supplementation has been identified as an effective therapy to slow disease progression, 5 we believe it is important for clinicians to be aware of this extremely rare, but potentially treatable syndrome within the spectrum of SPTLC1 ‐related disorders.…”

Dopamine transporter imaging versus myocardial MIBG scintigraphy for the diagnosis of prodromal synucleinopathies—and other updates on autonomic research

“…The January 22 2019 issue of Neurology includes the results of a randomized placebo-controlled trial of l-serine in patients with HSAN1 followed by a 1-year open-label treatment phase [6]. They recruited 18 patients randomized to l-serine (400 mg/kg/day) given in 3 doses or matching placebo.…”