The study, “A Phase 2A randomized, double-blind, placebo-controlled pilot trial of GM604 in patients with Amyotrophic Lateral Sclerosis (ALS Protocol GALS-001) and a single compassionate patient treatment (Protocol GALS-C),” appeared in the journal F1000 Research.
The data showed that treatment with GM6 improved ALS biomarkers — as well as clinical and functional measures in the ALSFRS-R (a scale that measures disease status) and FVC (a measure of respiratory capacity) — in ALS patients, including those with advanced forms of the disease.
GM6 is a synthetic drug containing six amino acids that act on multiple pathways crucial to the development of neurons and the human nervous system during the embryonic stage. These amino acids specifically bind to a group of insulin receptors (IGF1 and IGF2), activating pathways that regulate and repair the brain.
Previous work by Genervon showed that GM6 acts by regulating the activity of 89 genes involved in signaling pathways affected in ALS, such as neuronal generation, regulation of neuron death and regulation of oxidative stress-induced death in mitochondria, the cell’s powerhouse.
One of these genes is SOD1, a known ALS gene that accumulates in neurons, causing damage. According to the Pasadena, Calif.-based company, expression levels of SOD1 decreased with GM6 treatment in ALS patients.
“Our findings suggest a tentative tripartate mechanism of action by which GM6 could prolong motor neuron survival in ALS patients,” Genervon stated in a news release. “First, by reducing SOD1 expression, GM6 may block accumulation of pathologic SOD1 aggregates in motor neurons. Second, by reducing mitochondrial gene expression and potentially mitochondrial abundance (decreasing total tau), GM6 may disrupt the mitochondrial (intrinsic) apoptotic pathway. Third, GM6 appears to activate developmental/mitotic pathways (Cystatin C), which may promote cellular repair, axonogenesis, and neuron projection.”
Together, these results support GM6 as a promising new treatment for ALS, but more studies are necessary to confirm these effects. Genervon plans to open a Phase 3 ALS trial in the United States this year.