The Hereditary sensory neuropathy serine (SENSE) trial protocol

<h3>Introduction</h3> Hereditary Sensory Neuropathy type 1 (HSN1) is a rare autosomal dominant neuropathy marked by profound sensory and motor deficits, caused by variants in the SPTLC1/SPTLC2 genes. This leads to a gain-of-function mechanism in the serine palmitoyl transferase enzyme, and production of neurotoxic deoxysphingolipids, underlying the neuropathy. L-serine has shown potential as a treatment, but a previous study did not meet its primary outcome measure. Consequently, the lower limb MRI Muscle Fat Fraction protocol was developed as a highly responsive biomarker for HSN1. <h3>Objective</h3> Evaluate the efficacy of L-serine in treating HSN1 and validate the lower limb MRI Muscle Fat Fraction protocol as a primary outcome measure in inherited neuropathy trials. <h3>Methods</h3> This is a phase II, randomised, double-blind, placebo-controlled trial involving adults with a genetically confirmed SPTLC1/2 diagnosis and CMTES ≤ 26. Exclusion criteria include recent foot surgery, diabetes, pregnancy/breastfeeding, and current L-serine use. Participants will receive L- serine or dextrose powder 400mg/kg/day for 12-months. Primary outcome: difference in lower limb muscle fat fraction over 12-months between L-serine and placebo groups using MRI. Secondary measures include biomarkers, thigh intraepidermal nerve fibre density, and questionnaire-based assessments. <h3>Results</h3> Currently, 25 patients have completed screening. 15 have been randomised and recruited. <h3>Conclusion</h3> SENSE trial results will be presented at a future ABN meeting.