Turning up T-cells to tone down MND
It was five years ago when Associate Professor Brad Turner’s research career was transformed when speaking to the Inner Wheel and Rotary Clubs of Pakenham about his MND research at The Florey. He attracted the attention of the Stafford Fox Medical Research Foundation, who later invited him to submit a research proposal. He was subsequently awarded a $3 million research grant from the Stafford Fox Medical Research Foundation. Now in the final year of the grant, he and his team have made promising progress in their pursuit of developing effective treatment approaches for MND.
One key achievement from the Stafford Fox Medical Research Foundation grant was the exciting discovery that a specific type of immune cell, regulatory T-cells (Tregs), may help slow the progression rate of MND.
Tregs are part of the normal immune system and shut down harmful immune responses after eliminating invading organisms from the body. They also play a critical role in regulating other immune cells, preventing them from attacking healthy cells and tissues in the body by fighting inflammation. It is well known that inflammation builds up in the brain of MND patients, amplifying damage to motor neurons. Therefore, exploiting Tregs to fine-tune brain inflammation in MND seemed an innovative and exciting approach to Associate Professor Turner.
Associate Professor Turner and his team, in collaboration with neurologist Professor Steve Vucic at the Westmead Hospital, first demonstrated a significant relationship between Tregs and progression rate of MND in patients. The faster MND was progressing, the fewer inflammation fighting Tregs there were in blood. Likewise, the disease progressed more slowly in patients who had higher numbers of Tregs in their blood.
Intrigued by this observation, Associate Professor Turner and his team tested a new cocktail therapy to amplify Treg numbers in a mouse model of MND. They tested a chronic treatment which dramatically boosted spinal cord Treg levels – the major site of motor neuron death in MND. Importantly, the treatment protected motor neurons and dampened harmful inflammatory responses in spinal cord, resulting in a significant extension of lifespan in MND mice.
Associate Professor Turner said, “These results from MND patients and mice confirm the importance of Tregs in MND and demonstrate an effective therapeutic approach to suppress toxic inflammation in the spinal cord from the circulation.
“We are now keenly pursuing new strategies to boost Treg levels and protective activity in MND patients, with the ultimate goal of developing new therapies to effectively treat MND, as demonstrated by the current trial of Tecfidera in Australian MND patients.”
This study was the culmination of a national collaboration between the Florey, leading MND clinics, medical research institutes and universities, made possible by the Stafford Fox Medical Research Foundation. “The generous support of the Stafford Fox Medical Research Foundation has accelerated our research pace and fast-tracked candidate drug development for MND”, said Associate Professor Turner.
“This philanthropic funding has been transformative for my lab and expanded the research team and tools to aggressively tackle MND. We are extremely grateful for the tremendous support of the Stafford Fox Medical Research Foundation”.