Anton Reiner, PhD, professor in the Departments of Anatomy & Neurobiology, and Ophthalmology in the College of Medicine at the University of Tennessee Health Science Center (UTHSC), has received $1.35 million from the U.S. Department of Defense to study the benefits of the drug Raloxifene as a therapy to help reduce visual impairment stemming from retinal and optic nerve damage after mild traumatic brain injury or closed-globe ocular injury.
The award, which comes from the office of the Congressionally Directed Medical Research Programs, will be distributed over three years. The funds were awarded to Dr. Reiner, who is also Methodist Hospitals professor of Neuroscience and co-director of the UTHSC Neuroscience Institute, along with his UTHSC collaborators, Marcia Honig, PhD, of the Department of Anatomy & Neurobiology, and Bob Moore, PhD, of the Department of Pharmaceutical Sciences.
Visual deficits from traumatic brain injury and from non-rupturing ocular trauma by itself or in conjunction with brain injury are highly common in the military, often leading to an inability to return to service and/or lifelong impairments.
The study takes advantage of the recent discovery that Raloxifene, an FDA approved drug that is currently used to treat osteoporosis in women because of its action at estrogen receptors, also acts as an inverse agonist at CB2 receptors.
Dr. Reiner and his team will use two mouse models with visual deficits and retinal pathology mimicking what military members may experience as an outcome of combat, training or other service-related injury to test the benefits of Raloxifene.
Their previous research has found that treatment using a novel experimental cannabinoid type-2 (CB2) receptor inverse agonist developed by Dr. Moore significantly diminishes those deficits.
Unlike drugs that act on cannabinoid type-1 (CB1) receptors, such as marijuana, drugs that selectively target CB2 receptors do not have psychotropic effects. Instead, they modulate brain neuroinflammation by binding to a type of brain cell called microglia, converting them to a helpful rather than a harmful state.
“If our proposed animal studies show benefit of Raloxifene in preventing visual deficits and injury after brain and/or ocular trauma, it could be next tested in phase two human clinical trials, having already passed phase one safety testing,” Dr. Reiner said. “If proven effective in human clinical trials, it could soon have approval for use in military trauma victims.”
Therapies that limit the post-trauma visual impairments in patients with traumatic brain injury have not been identified, and current treatment options consist mainly of rehabilitation and/or corrective eyewear to mitigate the disability. By using Raloxifene in a treatment plan immediately after injury, Dr. Reiner hopes to reduce the amount of permanent damage caused by the injury, and thereby improve visual function and prevent disability. The study will determine if the drug shows enough promise in mice to be tested in humans.
“If approved for use in military trauma victims, Raloxifene could be adopted as a routine treatment administered by medical personnel shortly after trauma, and thereby prevent or reduce the harmful consequences of the trauma for vision,” Dr. Reiner said. “The drug would also be available for civilian use to limit the visual problems that stem from brain or eye trauma.”
The Congressionally Directed Medical Research Programs (CDMRP), is dedicated to advancing paradigm shifting research, solutions that will lead to cures or improvements in patient care, or breakthrough technologies and resources for clinical benefit. The CDMRP strives to transform health care for service members and the American public through innovative and impactful research. For more information about the CDMRP, visit http://cdmrp.army.mil.