Harnessing the Immune System to Treat TBI

Posted on October 29, 2022

Researchers have planned a targeted therapeutic treatment that restricts brain inflammation. The system intensifies the number of regulatory T cells in the brain, mediators of the immune system's anti-inflammatory response. The researchers were able to avert the death of brain tissue in mice following injury, and the mice performed better in cognitive tests by boosting the number of T regulatory cells in the brain. The treatment has a high possibility for use in patients with TBI, with few alternatives currently available to prevent harmful neuroinflammation.

A leading cause of this cognitive weakening is the inflammatory response to injury, with brain swelling causing lasting damage. While inflammation in other body parts can be controlled therapeutically, it is challenging in the brain due to the blood-brain barrier, which prevents common anti-inflammatory regulatory T cell molecules from getting to the trauma site. Anew therapy is underway to boost the population of regulatory T cells in the brain so they can manage and reduce the inflammation and damage caused by a brain injury.

Studies indicate that regulatory T cells were low in the brain because of an inadequate supply of the vital survival molecule interleukin 2, aka IL2. IL2 can't pass the blood-brain barrier; hence, levels are lower in the brain than in the rest of the body. Together, the team devised a novel therapeutic method that allows more IL2 to be made by brain cells, thereby providing the conditions required by regulatory T- cells to live. 

A 'gene delivery' system built on an engineered adeno-associated viral vector (AAV) was used. This system can cross an integral blood-brain barrier and deliver the DNA needed for the brain to produce more IL2. The blood-brain barrier has seemed like an insuperable hurdle to efficiently delivering biologics to the brain. Using the latest in viral vector technology, it is possible that the blood-brain barrier may be beneficial under certain circumstances, preventing the 'leak' of therapeutics to the rest of the body.

The new therapeutic developed by the research teams enhanced levels of survival molecule IL2 in the brain, up to 10-fold higher than normal im the blood.

To test the effectiveness of the treatment in a mouse model that closely bears a resemblance to TBI accidents, mice were given cautiously controlled brain impacts and then treated[AM1]  with the IL-2 gene delivery system. The scientists found that the treatment reduced the amount of brain damage following the injury, evaluated by comparing the mice's ability to perform cognitive tests and the loss of brain tissue. 

 Studying the mice's brains after the first experiment was a 'eureka moment' -- the treatment reduced the size of the injury lesion. Understanding and manipulating the brain's immune res[ponse, a gene delivery system for IL2 was developed as a possible treatment for neuroinflammation. 

With millions of people affected every year and scarce treatment options, this has real potential to help people in need. Clinical trials are awaited to test whether the treatment also works in patients.

Anti-inflammatory drugs work on the whole immune system and increase patients' susceptibility to such infections. The thrilling progress in this study is that the treatment can not only successfully reduce brain damage caused by inflammation but can do so without disturbing the rest of the body's immune system, thereby conserving the natural defenses needed to survive critical illness.