MDA is funding research into a potential treatment for amyotrophic lateral sclerosis (ALS) that inhibits excessive glutamate signaling in the brain and spinal cord.
The grant of $268,000 to Larkspur, Calif.-based Glialogix will enable the biotech firm to test its compound in mice with a disease that mimics a familial form of ALS caused by a mutation in the gene for the SOD1 protein. Glialogix is collaborating on the study with the ALS Therapy Development Institute (ALS TDI), a nonprofit biotech research institute based in Cambridge, Mass., that also receives funding from MDA.
“MDA is pleased to be able to support this important piece of research to determine the potential of GLX1112 for ALS,” said Jane Larkindale, director of MDA’s translational research program, which provided funding for the study. "We are happy to be able to bring together two valuable partners to get the drug tested in the best possible way in the preclinical model of ALS, so that we have strong data supporting or opposing future development."
Researchers believe that excessive signaling by glutamate, a central nervous system neurotransmitter, may play a role in neurodegenerative diseases such as ALS.
Glialogix has identified a new target that may be responsible for the excessive glutamate signaling observed in neurodegenerative diseases such as ALS. The target is on activated microglial cells, the immune-system cells in the central nervous system. Activated microglial cells are often found in neurodegenerative diseases, and the company believes it may be a link between inflammation in the nervous system and excessive glutamate signaling.
The Glialogix drug, called GLX1112, is designed to block the actions of this newly identified target. The Glialogix compound is a drug that has been on the market for decades but never used in neurological indications. The company intends to repurpose the compound for use in neurodegenerative diseases.
Riluzole (brand name Rilutek), the one drug approved by the U.S. Food and Drug Administration for the specific treatment of ALS, is also a glutamate inhibitor, but it works via a different mechanism than GLX1112. Rather than blocking a protein on microglial cells, it blocks specific glutamate receptors on nerve cells. Scientists hope that GLX1112 will prove to be more effective than riluzole, which has been shown to have only a modest effect on prolonging survival in ALS.
Using mice genetically engineered to have the SOD1-related familial form of ALS, Glialogix and ALS TDI scientists will test the safety and efficacy of GLX1112.
SOD1 mice are the most commonly used animal model for human ALS. Although they have a form of ALS that only affects 1 percent to 3 percent of patients with the disease, most experts believe there is considerable overlap in the cellular and biochemical changes that occur in the SOD1 form of ALS and in the nonfamilial (sporadic) form of ALS that affects the majority of individuals with the disease.
MDA’s support will be released in stages over the course of the year as certain milestones are achieved: evidence that the drug crosses the blood-brain barrier to reach the intended target; evidence that it is working to remove excess glutamate from the nervous system; and evidence that it is safe and well tolerated in the mice.
At the end of the year, results will be analyzed. If the drug reaches its target, is safe and has the intended effects, researchers at Glialogix plan to progress to testing the compound in more advanced animal models that require longer dosing regimens.
Should the new drug be found to work safely in animal models, this could lead to consideration of trials in humans.
Editor's note: This story was updated on 3/31/11 to clarify that the ALS TDI is a nonprofit biotech research institute.