Severe spinal cord injuries can have devastating and long-lasting effects on millions of people worldwide. While much of the damage is caused by degenerative processes following the initial trauma, researchers at Washington University School of Medicine in St. Louis have made significant progress in developing an immunotherapy to minimize this damage.
Their study, published in Nature, demonstrates the potential of immunotherapy in protecting neurons at the injury site from immune cell attacks, offering hope for improved outcomes for individuals recovering from spinal cord injuries.
“Immune cells in the central nervous system have a reputation for being the bad guys that can harm the brain and spinal cord,” said senior author Jonathan Kipnis, PhD, the Alan A. and Edith L. Wolff Distinguished Professor of Pathology & Immunology and a BJC Investigator at WashU Medicine. “But our study shows that it’s possible to take advantage of immune cells’ neuroprotective function while controlling their inherent detrimental abilities to help in the recovery from central nervous system injury.”
Following nervous system injury, a surge of immune cells converges on the site. This includes a mix of activated T cells, a subset of immune cells, that can either damage or shield neighboring neurons. Wenqing Gao, PhD, a postdoctoral research associate in the Department of Pathology & Immunology and the study’s primary author, conducted an analysis of T cells extracted from the spinal cords of injured mice.
She utilized genetic analysis to discern the distinguishing features of these cells. The objective was to segregate the harmful T cells from the protective ones and to replicate the beneficial cells for potential treatment of the injured mice.
Upon further examination, it was discovered that extended activation of protective T cells at the injury site could lead to unintended attacks on the body’s own tissues, resulting in autoimmune disease. To address this, Gao made adjustments to the cells, enabling them to deactivate after a limited time.
Mice treated with the modified T cells exhibited improved mobility compared to those left untreated. The greatest enhancements were observed when the T cells were administered within a week of the injury. Notably, none of the mice subjected to immunotherapy experienced any adverse autoimmune reactions.
“There are no effective treatments for traumatic injuries to the central nervous system,” explained Gao. “We developed immunotherapy for such injuries by taking advantage of the protective immune cells that infiltrate the injury site and found that it dramatically improved mobility in mice.”
A notable collaboration with WashU Medicine’s Dr. Wilson Zachary Ray, a distinguished spinal cord surgeon, revealed a remarkable finding. Over the course of a week, researchers diligently examined the cerebral spinal fluid of spinal cord injury patients, culminating in the discovery of a substantial increase in T cells. This finding underscores the potential to harness protective T cells from these patients for the development of groundbreaking immunotherapy.
“Our future goal is to devise a clinical trial to test the therapy in people with such injuries while expanding this work to neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) as well as Alzheimer’s and Parkinson’s diseases,” Gao said.
“Although the initial trigger in neurodegenerative diseases is different, the subsequent death of neurons may very well be mediated by similar processes, opening an opportunity for adapting our engineered cells for use as a therapy in neurodegeneration,” added Kipnis.
Journal reference:
- Wenqing Gao, Min Woo Kim, Taitea Dykstra, Siling Du, Pavle Boskovic, Cheryl F. Lichti, Miguel A. Ruiz-Cardozo, Xingxing Gu, Tal Weizman Shapira, Justin Rustenhoven, Camilo Molina, Igor Smirnov, Yifat Merbl, Wilson Z. Ray & Jonathan Kipnis. Engineered T cell therapy for central nervous system injury. Nature, 2024; DOI: 10.1038/s41586-024-07906-y
