Revolutionary Breakthrough: Modified Immune Cells Could Heal Spinal Cord Damag

modified immune cells spinal cord damage

Modified Immune Cells: New Treatment Cuts Spinal Cord Damage

Engineered Immune Cell Therapy Protects Compromised Neurons in Murine Models

Spinal cord trauma inflicts severe damage on nerve cells, disrupting the vital communication conduit between the brain and the peripheral body, thereby leading to lifelong disabilities affecting millions worldwide.

The immediate injury constitutes merely a fraction of the overall devastation inflicted upon the spinal cord, an extensive tissue structure stretching from the brain stem to the lumbar region.

A significant portion of the impairment arises from degenerative alterations localized at the injury epicenter.

Despite extensive investigations aimed at devising strategies to mend injured tissues, researchers at Washington University School of Medicine in St. Louis diverted their focus towards cultivating an immunotherapeutic approach in mice to mitigate the repercussions of traumatic spinal cord injury.

Their research reveals that immunotherapy can attenuate such damage by safeguarding neurons at the lesion site from immune cell-mediated assaults.

Published in Nature, the study underscores the efficacy of immunotherapy in treated mice and introduces an innovative methodology with the potential to enhance recovery prospects for individuals afflicted by spinal cord injuries.

modified immune cells spinal cord damage: Elucidating the Function of Immune Cells

“Immune cells within the central nervous system are often perceived as antagonists capable of inflicting harm on the brain and spinal cord,” stated senior author Jonathan Kipnis, PhD, the Alan A. and Edith L. Wolff Distinguished Professor of Pathology & Immunology and a BJC Investigator at WashU Medicine.

“However, our research demonstrates the feasibility of harnessing the neuroprotective properties of immune cells while regulating their innate detrimental capabilities to facilitate recovery from central nervous system injuries.”

Immediately following neural injury, immune cells inundate the affected area. This influx includes a heterogeneous population of activated T cells—a subset of immune cells—that can either inflict damage or confer protection to adjacent neurons.

Wenqing Gao, PhD, a postdoctoral research associate in the Department of Pathology & Immunology and the study’s lead author, meticulously analyzed T cells extracted from the spinal cords of injured mice, conducting genetic profiling to ascertain their identities.

Her objective was to distinguish the deleterious T cells from their protective counterparts and to proliferate the advantageous cells for therapeutic application in the injured mice.

Nevertheless, a significant challenge emerged. The protective T cells that migrate to the injury site possess the propensity to erroneously target surrounding tissues when activated for extended periods, potentially inducing autoimmune disorders.

To enhance the therapeutic safety profile, Gao engineered the cells to undergo self-termination after a few days.

modified immune cells spinal cord damage: Encouraging Outcomes and Future Aspirations

Mice administered the modified T cells exhibited superior mobility compared to their untreated counterparts. The most pronounced improvements were observed when T cell infusion occurred within a week post-injury.

Importantly, none of the mice subjected to immunotherapy developed any destructive autoimmune responses.

“There are currently no efficacious treatments for traumatic central nervous system injuries,” elucidated Gao. “Our immunotherapy leverages the protective immune cells that infiltrate the injury site, resulting in a significant enhancement of mobility in mice.”

In collaboration with Dr. Wilson Zachary Ray, MD, a spinal cord surgeon and the Henry G. & Edith R. Schwartz Professor of Neurosurgery at WashU Medicine, the research team monitored the presence of T cells in the cerebrospinal fluid of spinal cord injury patients daily for a week.

They detected a substantial proliferation of T cells, substantiating the potential to expand protective T cells from such patients for generating immunotherapy.

“Our forthcoming objective is to design a clinical trial to evaluate the therapy in individuals with spinal cord injuries, while also extending this research to neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), Alzheimer’s, and Parkinson’s diseases,” Gao stated.

Kipnis added, “Although the initial triggers in neurodegenerative diseases differ, the subsequent neuronal demise may be driven by analogous mechanisms, presenting an opportunity to adapt our engineered cells as a therapeutic intervention in neurodegeneration.”

Reference

“Engineered T cell therapy for central nervous system injury” by 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, and Jonathan Kipnis, 4 September 2024, Nature. DOI: 10.1038/s41586-024-07906-y

This research was funded by the BJC Investigators Program at WashU.