Dr. Michael J. Kubek, Ph.D., who was awarded this grant, has been doing research on thyrotropin releasing hormone (TRH) for the past three decades. The Army funded international research collaboration on suicidal ideation is the latest addition to his research.
TRH is known to have anti-depressant, anti-suicidal and anti-convulsant effects in humans. Because it cannot easily cross the “blood-brain barrier” the body uses to protect the brain, TRH is not very effective when taken orally or via an injection.
The anti-convulsant therapeutic effects has lead Dr. Kubek to also investigate the possibility of TRH serving as a non-invasive treatment for infantile spasms, a rare, uncontrollable form of epilepsy that affects six to 12 month old children.
Kubek and colleagues are trying to develop an intranasal nanoparticle drug delivery system where TRH or neuropeptides are introduced to the naval cavity. The naval cavity is an area where olfactory neurons can collect particles directly. The neuropeptides would be integrated into biodegradable nanoparticles that dissolve at a controlled rate. This approach is designed to send appropriate doses of the drug to the brain over a period of time.
Kubek developed an interest in the effects of TRH in a military setting after an encounter with Navy physician Captain Neal Naito several years ago. Dr. Naito had an interest in new treatment approaches for traumatic brain injury, post-traumatic stress disorder and suicide. Kubek was contacted by Dr. Naito and encouraged to seek out funding for future studies on TRH.
According to statistics found by the Pentagon and Department of Veterans Affairs, the suicide rate among active-duty military personnel has increased since 2004 to about one suicide everyday this year. The suicide rate is even higher among veterans. The IU School of Medicine project is one of the many ways research centers are trying to reduce the number of suicides in the nation’s military.
“These deaths are troubling and tragic,” said Dr. Kubek. “Today’s commonly used anti-depressants can take weeks to have an effect and carry a black box warning label for suicidal ideation in young adults. That is why we hope to develop a quick-acting, easy-to-use, non-invasive system that delivers a compound that’s been shown to reduce suicidal thoughts.”
The three-year research grant is an Applied Research and Advanced Technology Development Award, part of the Department of Defense’s Defense Medical Research and Development Program, funded by the Congressionally Directed Medical Research Program.
Abraham J. Domb, a professor of pharmacology at Hebrew University in Jerusalem, will be doing research alongside Dr. Kubek to develop an optimum nanoparticle-neuropeptide combination design to deliver the drug effectively. This process is expected to take about a year, after which testing on humans can begin.
Dr. Kubek will also be working with Purdue University researchers Stephen Byrn, Ph.D., Professor of Medicinal Chemistry Charles B. Jordan and Yoon Yeo, Ph.D., assistant professor, industrial and physical pharmacy.
Indiana University psychiatry professors Alan Breier, M.D. and Andrew Goddard, M.D. are expected to be directors of the clinical trials, which will be conducted the second and third year of the program. This process will be performed through the Clinical Research center of the Indiana Clinical and Translational Sciences Institute.
Dr. Kubek has worked with Indiana University Clinical and Translational Research and technology Corporation for many years and they support his new venture.
“Funding from Citizens United for Research in Epilepsy supported some of the proof of concept research for the intranasal nanoparticle delivery platform being used in the Defense Department grant,” said Dr. Kubek.