Researcher's 'magic bullet' for spinal cord injuries: Estrogen

Narendra Banik, Ph.D., has been studying spinal cord injuries at MUSC since 1976. His quest to better understand this debilitating injury has led to several breakthroughs in the field, including promising new treatments to halt or even reverse the progression of such injuries.

Banik recently received a $723,000 special initiative basic research grant from the Spinal Cord Injury Research Fund that will allow him to promote basic science research across the state, fueling the kind of breakthroughs he has been involved with for more than 40 years.

SCIRF was created in 2000 by the South Carolina state legislature to support spinal cord injury research and was funded by adding a $100 surcharge on each DUI conviction in the state. Since then, the fund has made possible everything from a statewide surveillance system designed to aggregate every new spinal cord injury in the state to quality of life assessments, clinical studies and the basic science research Banik says is fundamental to advancing the field.

“Our goal has been to find out what mechanisms and factors are involved in the breakdown of spinal cord tissue after traumatic injury,” Banik said. “If we understand these factors, then maybe we can think of agents that can protect the tissues and preserve their structures, which may promote at least a partial recovery.”

Banik’s work has led to the discovery that a calcium-activated enzyme called calpain is partly responsible for the destructive process of breaking down nerve tissue after a spinal cord injury.

“How this protease works is very similar to how papain works in tissue,” he explained. “Papain, as you know, is a meat tenderizer derived from the papaya fruit.”

Banik and an international team coined the name “calpain,” a portmanteau of calcium and papain, to describe it. They soon discovered that certain drugs could act as calpain inhibitors, slowing the destructive process and aiding in improvement of function.

“Unfortunately, we found that the destruction of tissue is not caused by any one thing,” he said. “There are many destructive pathways responsible for tissue degeneration. So treating just one of these pathways doesn’t do much. That means finding one agent that takes care of many of these pathways or using multiple agents in a combination therapy may be beneficial.”

The closest Banik has found to that “magic bullet” so far is something most people have probably heard of: estrogen.

“Estrogen is a multi-active hormone, and it takes care of many, many pathways,” he explained. “It’s a powerful antioxidant and anti-inflammatory. It acts as a growth factor, promotes micro-vessel growth and improves blood flow. Thus, estrogen may be a multi-active neuroprotectant.”

Naturally present in women as a sex hormone, Banik said estrogen’s remarkable healing ability could be linked to menstruation. “Estrogen has a critical angiogenic role in the physiology of the female reproductive system where recurrent neovascularization is a normal process,” he explained. “You need blood supply to protect cells and tissue. If the blood is not there, cells and tissue will die of ischemic damage. But estrogen protects against cellular death.”

Banik said animals that have undergone estrogen therapy after spinal cord injuries have typically seen a 25 to 30 percent increase in motor function.

Human safety trials for estrogen therapy have already begun, in collaboration with neurosurgeon Abhay Varma, M.D., and supported by a Clinical and Translational Science Award from MUSC. Banik said they are showing promise. His team is currently working on a new delivery method for estrogen, using nanoparticles to apply the very low doses of the hormone directly to the spinal cord, which may reduce the potential for side effects. Although more work needs to be done in this area, Banik hopes to apply for FDA approval for human trials related to that technique in the near future.

None of this would be possible, he said, but for the basic science research that has laid the groundwork for everything he’s done. “Without basic research, we can’t discover new therapies to test,” he explained. “Basic science drives the search for new therapeutic agents.”

Unfortunately, most private companies are reluctant to fund basic research, instead putting their money into projects that are more likely to pay off in the short term. Since the Great Recession began in late 2007, public money has evaporated as well. That leaves innovative initiatives like SCIRF to bridge the gap. SCIRF funds investigators conducting spinal cord injury research at universities across the state.

Banik hopes with SCIRF’s help, he can help build a thriving research culture across South Carolina.

“What I proposed is that, in order to maintain the continuity of basic science research in the state, we should train students from other colleges at MUSC,” he said. “My lab will act as a center where other colleges can send students interested in spinal cord injury research to be trained. And, they can take what they learn here back to their schools to continue their work there.”

Banik will start by accepting two masters or pre-doctoral students, who will be trained and supported for two to three months. He hopes the program will soon expand and that he’ll be able to accept more students once the program is up and running.

Findings from this basic science research will help identify agents that can be tested in the clinic – which will meet the goal of improving the health and quality of life of individuals with SCI in South Carolina, he said.

“Our goal is to help individuals with spinal cord injuries across the state,” Banik said. “Who knows what discoveries these students will make that can eventually be taken into the clinic?”