Efficacy of l‐Arginine treatment in patients with HTLV‐1‐associated neurological disease

OBJECTIVE: HTLV‐1 infection causes HTLV‐1‐associated myelopathy/tropical spastic paraparesis (HAM/TSP), resulting in loss of motor function. In this Phase 2 trial, we assessed the efficacy and safety of l‐arginine in patients with HAM/TSP. METHODS: This open‐label, single‐arm, Phase 2 study enrolled patients diagnosed with HAM/TSP. Patients received l‐arginine at a dose of 20 g orally for 1 week and were followed‐up for 3 weeks. The primary endpoint was change in walking speed in the 10‐m walk test (10MWT). The main secondary endpoints were change in Timed Up and Go Test (TUGT) time, improvement in inflammatory markers in cerebrospinal fluid (CSF), safety, and tolerability. RESULTS: The study enrolled 20 patients (13 [65%] female) with a mean age of 67.8 years (95% CI 62.3 to 73.3). Although the primary endpoint, the changes in 10MWT time between baseline (Day 0) and Day 7, did not reach statistical significance (mean percent change in time −3.5%, 95% CI −10.8% to 3.7%; P = 0.32), a significant improvement was detected between baseline and Day 14 (−9.4%, 95% CI −16.6% to −2.2%; P = 0.01). Significant improvements were also observed in selected secondary endpoints, including in TUGT time (−9.1%, 95% CI −15.5% to −2.7%; P < 0.01), and in neopterin concentration in CSF (−2.1 pmol/mL, 95% CI −3.8 to −0.5; P = 0.01). Adverse events were infrequent, mild, and resolved rapidly. INTERPRETATION: l‐arginine therapy improved motor function and decreased CSF inflammatory markers. l‐arginine thus represents a promising therapeutic option for patients with HAM/TSP. TRIAL REGISTRATION NUMBER: UMIN000023854.