Anavex Life Sciences Corp., a biopharmaceutical company focused on the development of new therapies for neurodegenerative and central nervous system (CNS) diseases, among others, recently announced the presentation of preclinical data for one of its lead drug candidates, ANAVEX2-73, as a multiple sclerosis (MS) treatment. The preclinical study’s lead investigator, Dr. Robert Lisak, will present a poster on the study’s results at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2016.
The poster, “Sigma-1 Receptor Agonists Inhibit Oligodendrocyte Cytotoxicity Induced by Molecules Involved in Cell Damage in Multiple Sclerosis,” will be presented on Friday, Feb. 19, by Dr. Lisak, an MD and professor of neurology at Wayne State University School of Medicine, Michigan.
MS is characterized by harmful pro-inflammatory damage to myelin, the lipidic material that protects the nerve fibers in the central and peripheral nervous systems. Demyelination, the process of myelin destruction, is a hallmark of MS, leading to progressive neurodegeneration and synaptic failure, with no current effective therapies to stop it.
Myelination, the process of myelin formation, is carried out by oligodendrocytes in the CNS. Although these cells do not proliferate or regenerate in the adult CNS, oligodendrocyte progenitor cells (OPCs) have been shown to migrate, proliferate, and partially remyelinate axons injured by MS lesions. As a result, pharmacologic agents that decrease or prevent the death of oligodendrocytes and OPCs, and protect them from damage by inflammatory agents present in MS lesions, are greatly needed.
Researchers have been focusing on the sigma-1 receptor (S-1R), a receptor upregulated during cellular stress and involved in calcium homeostasis, whose activation through agonists has been shown to have neuroprotective effects both in vitro and in vivo.
Dextromethorphan (DM), an approved S-1R agonist, is reported to protect oligodendrocytes in vitro from the harmful effects of a series of toxic agents, such as reactive oxygen species (ROS) and glutamate. In this study, the team investigated if ANAVEX2-73, a S-1R agonist chemically unrelated to DM, also had a protective effect on oligodendrocytes. ANAVEX2-73 is a clinical stage compound currently being assessed in a Phase 2a trial for Alzheimer’s disease treatment.
Researchers prepared cell cultures enriched with oligodendrocytes from newborn rat brains. These cultures were incubated with different concentrations of ANAVEX2-73 and exposed to different toxic molecules. Through analysis of cell death, they observed that, after exposure to any of the toxic molecules, ANAVEX2-73 reduced oligodendrocyte cell death by over 50 percent.
According to the meeting’s abstract, the research team concluded, “Studies to determine the relative roles of S-1R agonism (…) are objectives for future studies. ANAVEX2-73 and DM are small molecules that enter the central nervous system and thus have potential to provide protection of OL [oligodendrocytes] in MS.”
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