The NTI MND Research Grant – Update May 2019 – MND and Me Foundation

The NTI MND Research Grant – Update May 2019

Recipient:  Associate Prof Trent Woodruff

Therapeutic Targeting of the Immune System in Motor Neuron Disease

Our laboratory is investigating the role of the immune system in motor neuron disease (MND). Immune cells are normally involved in protecting us from infections, but we have evidence that these immune processes are ‘accidently’ switched on in patients with MND. In our recent experiments using donated blood samples, we have discovered that certain populations of white blood cells are over-activated in MND patients. A key pro-inflammatory immune receptor, called C5aR, is also elevated on these immune cells. Importantly, our prior work in animal models of MND showed blocking this receptor with our drug, PMX205, could improve muscle strength and extend survival. This suggests that inhibiting C5aR with PMX205 may also be able to slow disease progression in MND patients.

To achieve this goal, we are working with the Queensland pharmaceutical company, called Alsonex Pharmaceuticals. Together, we are now progressing PMX205 into human clinical trials.

We have demonstrated that PMX205 is safe in preclinical toxicology studies and are planning a Phase I safety trial to run 2019. This trial will first include healthy subjects to determine the blood concentrations of PMX205 and assess any safety concerns. We can then progress into testing the drug in MND patients, which is aiming to start in 2020.

In our other research, we are investigating additional components of the immune system in MND, and have identified several exciting components that could be potential therapeutic targets. One of these is an immune receptor called FFAR2, and we are examining its role in human MND blood immune cells and in MND mouse models. Another is an immune component called complement C5. We are working with pharmaceutical companies to develop drugs that can target these immune molecules. We are hopeful that in the coming years we may be able to progress several new drugs into MND clinical trials to make a real impact on this disease. We are very grateful for the support of the MND community and the MND & Me Foundation for their support of our research.