Last year, Mark Mahan, MD, professor of neurosurgery, received a prestigious R01 grant from the National Institutes of Health for his research on pathophysiologic nerve regeneration. Fewer than 3% of practicing neurosurgeons in the US were awarded R01 grants over a recent 24-year period, so his receipt of the grant as the sole Principal Investigator on the project is quite extraordinary.
Dr. Mahan’s research examines the innate ability of nerves to regenerate over long distances such
as the gaps created during trauma. Despite this inherent capacity, nerve regeneration often fails—particularly in the severe peripheral nerve injuries that Dr. Mahan treats in his clinic. These severe peripheral nerve injuries lead to neuromas or exuberant scar tissue within the nerve, physiologically and physically blocking regeneration pathways and leaving many patients without functional use of their limb.
In an effort to better understand how the natural regenerative process is corrupted in severe nerve injuries, Dr. Mahan and his team have set out to evaluate neuroma formation. Specifically, they are investigating whether or not an aggressive form of inflammation involving neutrophil extracellular trap (NET)osis cell death is an inciting cause of neuroma formation. Preliminary data have shown that NETs only form in severe injuries that develop neuromas. The basis of the grant is to manipulate NET products to see whether this cascade is the critical event that produces neuromas.
If this is indeed the case, Dr. Mahan and his laboratory team intend to examine whether the products of this inflammatory cascade can be treated with DNase I—an enzyme that separates DNA and oligonucleotide products—to determine whether or not nerve regeneration can be improved. Preliminary evidence supports that nerve health is improved when the NET products are cleared after injury. If the study is successful, the team hypothesizes that there might be a novel treatment for flipping the environment after injury—from one destined to fibrosis and scar tissue to one that promotes healthy nerve regeneration.
“The preliminary evidence is very promising,” Dr. Mahan shared, “and we’re hopeful that this study will lead to breakthroughs in our understanding of nerve regeneration after severe injuries. Giving people back use of their arm or leg is among the most rewarding of experiences I have had. Increasing our ability to restore function even more will be a life changer—for me and every one of my patients.”
