Abstract: Biomarkers are not as commonly used in ALS drug development as in the drug development process for oncology. Biomarkers are important component of the ALS drug development pathway to demonstrate drug effect and target engagement. In a recent Phase 2A double-blind, randomized, placebo controlled clinical trial with GM604 (AKA MNTF, GM6), where ALS patients were treated with six doses of GM604 for two weeks and then continued to be evaluated for disease progression until 10 weeks after cessation of GM604 treatment, it was demonstrated that GM604 can modulate expression of ALS disease related genes, through pathways that bring about homeostasis of pertinent ALS biomarkers. The statistical significance in biomarker changes also correlate with treatment effects in clinical observations.

Abstract: One aspect of this study was to provide a bioinformatic analysis to assess whether the MNTF-derived peptide known as GM6 alters the expression of genes associated with Alzheimer's disease. Gene expression analyses are performed using several gene expression profiling datasets generated by DNA microarray or RNA-seq technology. Our results show Alzheimer's disease-associated genes exhibit unique responses to GM6 treatment, impacting signaling pathways linked to core processes that underlie Alzheimer's disease onset and progression. The expression of one or more genes or gene variants of particular interest described herein. We show that ALS patients treated with GM6 exhibit significantly decreased abundance of plasma tau post-treatment (FIG. 1D). We also show that GM6 repressed MAPT mRNA in SH-5YSY cells (FIG. 2).