2025 American Academy of Neurology Abstract Website

Objective:

To determine the safety profile of Arimoclomol in patients with Amyotrophic Lateral Sclerosis (ALS).

Background:

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by muscle weakness and respiratory failure. Arimoclomol, a co-inducer of heat-shock protein-70 (HSP70), has shown neuroprotective effects in animal models of ALS by promoting the clearance of protein aggregates, a key pathological feature of both sporadic and familial ALS.

Design/Methods:

PubMed, Cochrane Central, and Embase were searched till September 2024. Risk Ratios (RR) along with the 95% Confidence Interval (CI) were pooled for dichotomous outcomes using the Review Manager 5.4.1 under the random effects model. The primary safety endpoint is serious adverse events. The secondary safety endpoints are respiratory, upper gastrointestinal (GI), lower GI, cardiac (CV), and musculoskeletal (MSK) adverse events along with mood symptoms. Quality assessment was done using the Cochrane Risk of Bias (RoB 2.0) tool. A sensitivity analysis was conducted for heterogeneity.

Results:

Three randomized clinical trials pooling 319 patients were included in this meta-analysis. Arimoclomol was comparable to placebo regarding the serious adverse events (RR=0.75; 95%CI:[0.41,1.37]; p=0.35; I²=44%), respiratory (RR=1.36; 95%CI:[0.47,3.92]; p=0.57; I²=70%), upper GI (RR=1.87; 95%CI:[0.24,14.36]; p=0.55; I²=93%), and lower GI adverse events (RR=1.51; 95%CI:[0.89,2.54]; p=0.12; I²=0%). The was also no significant difference in terms of CV (RR=1.64; 95%CI:[0.57,4.72]; p=0.35; I²=19%), MSK adverse events (RR=1.82; 95%CI:[0.81,4.05]; p=0.14; I²=45%) and mood symptoms (RR=0.88; 95%CI:[0.26,2.95]; p=0.83; I²=81%) between the treatment and the control group in ALS patients.

Conclusions:

The meta-analysis concluded that Arimoclomol appears to have a comparable safety profile to placebo in patients with ALS, with no significant differences in the incidence of serious adverse events, including respiratory, gastrointestinal, cardiac, musculoskeletal, and mood-related symptoms. The findings suggest that Arimoclomol is generally well-tolerated in ALS patients, though further studies may be needed to confirm these results.