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Early Investigation of Novel ALS Treatment

Safety, Pharmacokinetic, and Functional Effects of the Nogo-A Monoclonal Antibody in Amyotrophic Lateral Sclerosis: A Randomized, First In-Human Clinical Trial

Meininger, V, Pradat, PF, Corse, A, et al. PLOS One
Submitted by Nicholas Johnson, MD, News Science Editorial Board

This study investigates the use of an antibody against a protein called Nogo-A in patients with amyotrophic lateral sclerosis (ALS). Nogo-A is a negative regulator of neurite outgrowth expressed by oligodendrocytes. Earlier work had previously identified Nogo-A to be over-expressed by a mouse model of ALS and in humans with ALS. An antibody to this protein, Ozanezumab, has been developed to act against this protein. Of note, this protein is not well expressed in individuals without ALS. Therefore, the investigators decided to proceed with Phase I safety studies in individuals with ALS.

In this study, there were two phases. In part one, individuals received a single, escalating dose of the antibody to evaluate safety. In part two, three cohorts of 12 each received two doses of Ozanezumab or placebo, randomized 3:1, separated by four weeks. Safety evaluation showed several common adverse events, including back pain, headache, or procedural site pain. No adverse event was severe enough to withdraw from the study. The drug half-life was approximately 20 days. On deltoid muscle biopsies, the antibody co-localized with Nogo-A in the highest dose cohort. One of the subjects in the highest dose category did show an immunogenic response to Ozanezumab. This is a learning phase study, and, therefore, it is not powered to understand the efficacy of the treatment. The investigators did look at changes in the ALSFRS-R and the percent of predicted SVC percentage. There was not a statistical difference between the treatment and placebo groups, though there was a numerical difference favoring the treatment group.

This learning phase study investigates a novel treatment for ALS. Ozanezumab is a new approach to addressing this devastating disease. Based on this study, it appears to be reasonably safe and worth proceeding with additional study. Given the difficulty identifying successful treatments for ALS in the past, there should be cautious optimism that this therapy may not suffer the same fate.

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