Severe spinal cord injuries affect millions of people worldwide, often resulting in long-term and debilitating consequences. Much of the damage comes not only from the initial trauma but also from degenerative processes that follow. However, researchers at Washington University School of Medicine in St. Louis have made remarkable progress in developing an immunotherapy that may help minimize this secondary damage. Their study, published in Nature, highlights how immunotherapy could protect neurons at the injury site from harmful immune cell attacks, providing new hope for improving recovery outcomes in individuals with 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,” explained Jonathan Kipnis, PhD, the Alan A. and Edith L. Wolff Distinguished Professor of Pathology & Immunology at WashU Medicine. “But our study shows it’s possible to harness the neuroprotective functions of these cells while controlling their harmful tendencies to aid in the recovery from central nervous system injuries.”

Following nervous system trauma, immune cells rapidly converge on the injury site. These include activated T cells, which can either damage or protect nearby neurons. Wenqing Gao, PhD, the study’s lead author and a postdoctoral research associate in the Department of Pathology & Immunology, conducted an analysis of T cells extracted from the spinal cords of injured mice. Her goal was to identify and separate the harmful T cells from the protective ones, enabling the beneficial cells to be replicated for potential therapeutic use.

However, the researchers found that if protective T cells remained active at the injury site for too long, they could start attacking the body’s tissues, leading to autoimmune diseases. To counter this, Gao engineered the cells to deactivate after a limited period, reducing the risk of harmful side effects.

In tests on mice, those treated with the modified T cells showed significant improvement in mobility compared to untreated mice, particularly when the therapy was administered within a week of the injury. Importantly, none of the treated mice exhibited any signs of autoimmune reactions, indicating the safety of the treatment.

“There are no effective treatments for traumatic injuries to the central nervous system,” said Gao. “Our immunotherapy takes advantage of the protective immune cells that gather at the injury site, and we found it dramatically improves mobility in mice.”

In collaboration with Dr. Wilson Zachary Ray, a spinal cord surgeon at WashU Medicine, the researchers also studied patients with spinal cord injuries. Over the course of a week, they analyzed the patients’ cerebrospinal fluid and observed a notable increase in T cells. This discovery suggests the possibility of using protective T cells from these patients for further developing the immunotherapy.

“Our long-term goal is to design a clinical trial to test this therapy in people with spinal cord injuries,” Gao said. “Additionally, we want to expand this work to neurodegenerative diseases like ALS, Alzheimer’s, and Parkinson’s, where similar processes could be at play.”

Kipnis added, “While the initial triggers in neurodegenerative diseases differ, the resulting neuron death may be mediated by similar mechanisms, creating an opportunity to adapt our engineered cells for use in treating these conditions.”

By Impact Lab