The 24 hours following a traumatic spinal cord injury are the most critical to the long-term quality of life for patients, including those with incomplete spinal cord injuries – injuries in which the spinal cord can send some messages to or from the brain and patients have some feeling and muscle control below the injury site.
According to a research team at Wayne State University, a critical challenge in addressing incomplete spinal cord injury is to devise an effective intervention during that 24-hour window that positively impacts long-term functional mobility. Drug therapies have shown to be ineffective because they must be delivered through the bloodstream — causing a significant delay for building up efficient concentrations at the target site — and must cross several membrane systems (i.e., blood spinal cord barrier). This delay affects the prospects of saving and regenerating neurons at the injury site.
To help address this situation, a collaborative research team from Wayne State University received a five-year, nearly $2.8 million grant from the National Institute of Neurological Disorders and Stroke of the National Institutes of Health for the study, “Non-invasive infrared light therapy and medical device to treat spinal cord injury.” The co-principal investigators include Moh Malek, Ph.D., professor of Physical Therapy in the Eugene Applebaum College of Pharmacy and Health Sciences, and Maik Hüttemann, Ph.D., professor of Molecular Medicine and Genetics, and of Biochemistry, Microbiology and Immunology, in the School of Medicine.
“Mitochondria are often referred to as the ‘powerhouses of the cell’ because that is where more than 90% of the cell’s energy is generated,” Dr. Hüttemann said. “Thus, disruptions to the mitochondria can negatively influence energy production, which causes the cells to function improperly. Such is the case with traumatic spinal cord injury, where the mitochondria initially become hyperactive and, therefore, produce large amounts of damaging reactive oxygen species or ‘free radicals,’ leading to a cascade of events that trigger the death of nerve cells.”
Dr. Hüttemann pioneered the development of an infrared light device that has received multiple patents and forged a start-up called Mitovation. Whereas most commercially available infrared light systems increase mitochondria activity, the wavelengths he discovered reduce mitochondria activity.
“The idea of starting this research came from watching the National Institutes of Health conference SCI 2020: Launching a Decade for Disruption in Spinal Cord Injury Research, which, in part, focused on a critical need to develop new and innovative treatment strategies for the initial 24 hours following injury to the spinal cord,” Dr. Malek said. “Occasionally, a fresh perspective from people outside the research area is needed to examine a problem and develop a potential solution. While neither Maik nor I are spinal cord injury researchers, we have a 14-year history of collaboration related to mitochondria function. Thus, using the infrared light technology presented a unique opportunity to potentially treat incomplete spinal cord injury in the initial 24 hours following the trauma.”
The project will use the patented non-invasive infrared light technology to target mitochondria in the injured spinal cord. The goal is to decrease the reactive oxygen production, which is detrimental to neuronal cell regeneration.
“This research project is an excellent example of taking a university-created technology and applying it to a different need in hopes of creating therapies not once thought of,” said Ezemenari Obasi, Ph.D., vice president for Research & Innovation at Wayne State University. “Drs. Malek and Hüttemann have thought of a creative new approach that may one day give us answers to key gaps in spinal cord research that ultimately could help many.”
Using a team science approach, Drs. Malek and Hüttemann, along with their co-investigators and consultants Drs. Dennis Goebel (WSU School of Medicine), Dragana Komnenov (WSU School of Medicine), Wassim Tarraf (WSU Eugene Applebaum College of Pharmacy and Health Sciences), Gerry Hish (University of Michigan-Ann Arbor), Thomas Sanderson (University of Michigan-Ann Arbor), Linda Noble Haeusslein (University of Texas, Austin) and Victor Chang (Henry Ford Health), will perform a series of longitudinal experiments and ultimately develop a prototype of their infrared light delivery system for human application as part of this grant.
“At the end of five years, we will be ready to propose a Phase I clinical trial study that can determine critical next steps for this potential treatment,” Drs. Malek and Hüttemann said.
The grant number for this National Institute of Neurological Disorders and Stroke of the National Institutes of Health research study is NS134695.