The Safety and Efficacy of Arimoclomol in Amyotrophic Lateral Sclerosis: A Systematic Review (P11-11.029).

OBJECTIVE: To assess the efficacy and safety of arimoclomol in patients with Amyotrophic Lateral Sclerosis (ALS). BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a progressive and fatal neurodegenerative disorder that primarily affects the motor neurons in the motor cortex, spinal cord, and brainstem. Ongoing research is focused on developing therapeutic strategies to modify the disease's progression, with Riluzole being the drug currently shown to extend survival. Among emerging therapeutic options, Arimoclomol has demonstrated benefit in preclinical studies. It acts as a co-inducer of heat shock protein-70 (HSP70) and aims to enhance the clearance of misfolded proteins, a hallmark of sporadic ALS pathology. DESIGN/METHODS: We conducted a Systematic Review searching PubMed, Embase, and Cochrane databases until September 2024. Randomized controlled trials (RCTs) that assessed the safety and efficacy of Arimoclomol were included. Efficacy was assessed on change on the ALSFRS-R scale, and safety was evaluated through adverse events. We excluded animal models from our review. RESULTS: Three studies encompassing 367 patients were analyzed. Evaluation of the ALSFRS-R scores indicated non-significant improvements in studies with lower drug dosages, whereas no differences were observed in the ORARIALS-01 between treatment groups. In two of these studies, adverse events were generally mild and unrelated to the drug. However, the ORARIALS-01 study observed a higher treatment discontinuation rate attributed to the drug. Reported adverse events included dyspnea, nausea, anorexia, vomiting, duodenal ulcer, muscle weakness, pain, anxiety, depression, headache, gastrostomy tube complications, apnea, and coronary artery disease. CONCLUSIONS: Current data do not support the use of Arimoclomol for patients with ALS. Although the drug has been demonstrated to be neuroprotective in animal models, this characteristic was not reproducible in patients with ALS and did not significantly change the disease course. Further studies should be conducted to evaluate its possible efficacy in specific groups of patients. Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff. Disclosure: Miss Barbosa has nothing to disclose. Mr. De Sousa Marinho Mendes Filho has nothing to disclose. Mr. Abraham has nothing to disclose. Miss Weba has nothing to disclose. Mr. NOGUEIRA has nothing to disclose.