May 26, 2022

Harnessing the Immune System to Treat Traumatic Brain Injury in Mice

Article published by ScienceDaily

A therapeutic method for harnessing the body’s immune system to protect against brain damage is published today by researchers from the Babraham Institute’s Immunology research programme. The collaboration between Professor Adrian Liston (Babraham Institute) and Professor Matthew Holt (VIB and KU Leuven; i3S-University of Porto) has produced a targeted delivery system for boosting the numbers of specialised anti-inflammatory immune cells specifically within the brain to restrict brain inflammation and damage. Their brain-specific delivery system protected against brain cell death following brain injury, stroke and in a model of multiple sclerosis. The research is published today in the journal¬†Nature Immunology.

Traumatic brain injury, like that caused during a car accident or a fall, is a significant cause of death worldwide and can cause long-lasting cognitive impairment and dementia in people who survive. A leading cause of this cognitive impairment is the inflammatory response to the injury, with swelling of the brain causing permanent damage. While inflammation in other parts of the body can be addressed therapeutically, but in the brain it is problematic due to the presence of the blood-brain barrier, which prevents common anti-inflammatory molecules from getting to the site of trauma.

Prof. Liston, a senior group leader in the Babraham Institute’s Immunology programme, explained their approach: “Our bodies have their own anti-inflammatory response, regulatory T cells, which have the ability to sense inflammation and produce a cocktail of natural anti-inflammatories. Unfortunately there are very few of these regulatory T cells in the brain, so they are overwhelmed by the inflammation following an injury. We sought to design a new therapeutic to boost the population of regulatory T cells in the brain, so that they could manage inflammation and reduce the damage caused by traumatic injury.”

The research team found that regulatory T cell numbers were low in the brain because of a limited supply of the crucial survival molecule interleukin 2, also known as IL2. Levels of IL2 are low in the brain compared to the rest of the body as it can’t pass the blood-brain barrier.

Together the team devised a new therapeutic approach that allows more IL2 to be made by brain cells, thereby creating the conditions needed by regulatory T cells to survive. A ‘gene delivery’ system based on an engineered adeno-associated viral vector (AAV) was used: this system can actually cross an intact blood brain barrier and deliver the DNA needed for the brain to produce more IL2 production.

Commenting on the work, Prof. Holt, from VIB and KU Leuven, said: “For years, the blood-brain barrier has seemed like an insurmountable hurdle to the efficient delivery of biologics to the brain. Our work, using the latest in viral vector technology, proves that this is no longer the case; in fact, it is possible that under certain circumstances, the blood-brain barrier may actually prove to be therapeutically beneficial, serving to prevent ‘leak’ of therapeutics into the rest of the body.”