Genervon Biopharmaceuticals has published a list of 89 genes associated with amyotrophic lateral sclerosis (ALS) that are modulated by its drug candidate GM6. The identification of the genes regulated by GM6 helps to explain the mechanism of action of this treatment, which aims to improve neuronal repair and survival, and restore their proper function.
This information was presented at the 35th Annual JP Morgan Healthcare Conference, held in San Francisco on Jan 9–12.
Many clinical trials for ALS have failed because conventional drugs are designed to target a single gene or protein. This narrows down the efficiency of the drug because, in people whose brains are affected by ALS, several pathways are disrupted. By targeting several genes, GM6 may be a promising therapy approach that tackles different disease-associated pathways at the same time.
GM6 is a synthetic drug containing six amino acids that act on multiple pathways that play an important role in the development of neurons and the human nervous system during the embryonic stage. These amino acids specifically bind to a group of receptors, called the insulin receptors (IGF1 and IGF2 receptors), thereby activating pathways that regulate and repair the brain.
Several laboratory analyses showed that GM6 regulates the activity of 89 genes that have been previously associated with ALS. These genes are involved in signaling pathways that include neuronal generation, regulation of neuron death, and the regulation of oxidative stress-induced death.
They also found that GM6 helps to lower expression levels of SOD1, a known ALS gene. Previous studies have shown that mutations in the SOD1 gene account for 20 percent of inherited ALS cases, but misfolded versions of the SOD1 protein may also lead to the development of this disease.
Results obtained while studying the impact of GM6 treatment in the genetic profile of neurons support that this drug has a three-part mechanism of action. That mechanism includes: reducing SOD1 expression (avoiding its toxic accumulation in motor neurons), protecting the mitochondria (the cells’ powerhouse), and activating neuronal repair, growth and maturation. Details of the study can be found here.
GM6 was developed to target several neurological disorders, such as ALS, Parkinson’s, Alzheimer’s and Huntington’s diseases. It has been shown to have a safe profile in a Phase 1 and three Phase 2 trials with patients with ALS, Parkinson’s and stroke.
According to Genervon, a Phase 3 trial for ALS is expected to start this year.