Researchers from the San Francisco Veterans Affairs Medical Center and UCSF, and CalciMedica, Inc., are presenting a poster at the 46th annual Society for Neuroscience meeting in San Diego describing the use of calcium release-activated calcium (CRAC) channel inhibitors in traumatic brain injury (TBI). The poster, to be presented on Wednesday, November 16th, is titled "Calcium release-activated calcium (CRAC) channel inhibition protects against experiment brain injury by inhibiting microglial activation". It indicates that a CRAC channel inhibitor developed by CalciMedica protected neurons in association with microglia, both in vitro and in vivo, to various insults, including oxygen deprivation, immune activation with pro-inflammatory agents and blunt force trauma, through modulation of microglia. In the TBI model, the CRAC channel inhibitor decreased lesion size, brain hemorrhage and neurological deficits.
Midori Yenari, MD, Professor in the Dept. of Neurology at UCSF School of Medicine and the San Francisco VA Medical Center Neurology Dept. and senior author of the paper, said "This work potentially opens up a new approach to modulate the acute inflammation that can be so damaging in neurological emergencies like TBI and stroke. We are excited about expanding this work, better characterizing the effects of these compounds in our disease models, and hopefully making the transition to human studies, where the need for effective therapies is so great."
Microglia are immune cells that reside in the central nervous system; they are similar to macrophage cells in other tissues. They are typically quiescent, but support and protect neurons when activated by scavenging extracellular debris, including dead or dying cells, and bacteria and viruses. They can release cytotoxic substances like H2O2, or release cytokines to either directly kill bacteria or mount an immune response against them, but this can also injure neurons if uncontrolled. It is hypothesized that during and shortly after brain trauma, activated microglial cells contribute to the injury, and by limiting this response, damage can be reduced.
Sudarshan Hebbar, Senior Vice President, Clinical Development at CalciMedica, said, "Our collaboration with Dr. Yenari has been very gratifying, as she is an expert in neuroinflammation, an area in which we think CRAC channel inhibitors may have a role to play. She is also an accomplished translational researcher, which is important as we think about next steps." Ken Stauderman, Senior Vice President, Research at CalciMedica, added, "We hope to look at the effects of these compounds in both acute and chronic neuroinflammation, which are components of many serious neurological disorders and diseases, first in animals and then potentially in patients."