James D. Lechleiter, Ph.D., professor of cellular and structural biology in the School of Medicine at The University of Texas Health Science Center at San Antonio, received a U.S. Patent December 31, 2013 for his discovery that a class of molecules is protective against traumatic brain injury (TBI). The patent, No. 8,618,074, covers novel methods for treating and preventing neuronal damage. He is continuing his work on development of potential treatments for TBI based on his invention. His findings in cell and animal models have been reported in peer-reviewed journals. Studies not published yet extend the results to human brain tissue taken from patients who underwent temporal lobectomies to inhibit treatment-resistant epilepsy. The patent application was filed in 2007.
Lechleiter worked closely with the Health Science Center’s Office of Technology Transfer and Commercialization (OTTC). He notes, “OTTC was invaluable in shepherding my application through the patenting process. They really championed the patent at critical junctures.”
Lechleiter discovered two compounds (2-methylthio-ADP and MRS2365) that stimulate astrocytes (caretaker cells) to do their work. These molecules are purinergic receptor ligands. Lechleiter notes: “Normally people want to block things to stop injury. We’re saying let’s stimulate the natural caretakers of the brain, part of whose job is to help control edema.” Edema is a serious consequence of TBI. Fluid build up from injury increases pressure inside the skull which causes brain tissue compression.
Dr. Lechleiter and Murat Digicaylioglu, M.D., Ph.D., associate professor of neurosurgery in the School of Medicine, had previously shown that after an injury to mouse brain, treatment of astrocytes with 2-methylthio-ADP and MRS2365 significantly reduced edema. Lechleiter notes, “With this treatment, astrocytes themselves, as well as neurons, live longer. It is hoped these preliminary studies will soon lead to a new class of safe and effective drugs that can be administered if a traumatic brain injury, even a mild one, is suspected to have occurred.”
External symptoms of TBI do not always present themselves and may go unnoticed in stressful situations such as car accidents and sports injuries. Given that the skull doesn’t have the ability to expand, excess fluid pushes against the brain pushing it aside which in turn places pressure on neurons and other tissues.
Lechleiter notes that undiagnosed TBIs are like time bombs because the injury is progressive. Many times people don’t realize they are having problems because sometimes it takes time to manifest itself. Consider soldiers wounded in war where their trauma may have happened in Afghanistan and they are unaware of it and end up carrying it home with them.
Lechleiter is currently working with the Center for Innovation in Drug Discovery, a joint center of the Health Science Center and The University of Texas at San Antonio, to refine and further develop purinergic receptor-based medications for people with TBI.
Once pre-clinical studies have been carried out, potential drugs that stimulate astrocytes will be brought into Phase I clinical trials to begin testing therapeutic potential and safety. Generally, this phase of development is done in partnership with pharmacology companies or spun out into a start-up company. OTTC is working closely with Lechleiter to identify the next best step.
Lechleiter notes, “Our most recent results indicate that purinergic ligand treatment of TBI also eliminates the long-term neurological deficits typically associated with repetitive head injuries. We’re very excited about the clinical impact of these findings and hope this success leads to new drug therapies for people with multiple brain injuries.”