MND and Me Fat Rabbit Research Grant – Update Nov 2017

Recipient:  Associate Prof Trent Woodruff

Woodruff Laboratory members 2017 L-R Samantha Levin, Trent Woodruff, John Lee and Angela Hanton

The role of the immune system in driving the progression of motor neuron disease (MND): Discovery of new therapeutics

The Woodruff Laboratory is investigating the role of the immune system in MND. We have discovered that several immune proteins that are normally involved in protecting us from infection, are increased in patients with MND.

We are exploring whether inhibiting these specific immune factors may be able to slow the progression of MND using cellular and animal models of MND. Ultimately, we hope to identify and develop new drugs that may slow or halt MND progression.

One of our primary “targets” is an immune factor called complement C5a, which is a very potent mediator of inflammation. We have shown that C5a and its receptor, C5aR, are increased in the bloodstream of MND patients, as well as in the blood and spinal cord of MND rodent models. Several years ago a drug, called PMX205, was developed at The University of Queensland which blocks C5aR.

In 2017, we completed our studies testing this drug in the SOD1G93A mouse model of MND. Our results demonstrated that mice receiving PMX205 either before, or after disease onset, had extended survival, increased muscle strength and slower disease progression. This tightly controlled preclinical efficacy study promotes PMX205 as a potential future therapeutic for MND.

We are now working with a new pharmaceutical company (Alsonex Pharmaceuticals) that is aiming to progress PMX205 into human clinical trials for MND. Before we can do this, we need to assess the safety profile of PMX205 in what is termed “formal preclinical studies” (see PMX205 clinical progression diagram above). Alsonex has manufactured large quantities of PMX205 to use in these safety (toxicology) studies. The studies will involve administering PMX205 to several animal species to assess for any side-effects of drug administration, and will be completed in 2018. Importantly, to date, no major side effects have been observed.

We are now working with a new pharmaceutical company (Alsonex Pharmaceuticals) that is aiming to progress PMX205 into human clinical trials for MND. Before we can do this, we need to assess the safety profile of PMX205 in what is termed “formal preclinical studies” (see PMX205 clinical progression diagram below). Alsonex has manufactured large quantities of PMX205 to use in these safety (toxicology) studies. The studies will involve administering PMX205 to several animal species to assess for any side-effects of drug administration, and will be completed in 2018.

Importantly, to date, no major side effects have been observed.

We have also begun investigating other components of the immune system in MND, and have identified several exciting components that also seem to be increased in MND patients.

We are now working towards identifying drugs which can block these other immune proteins and testing them in our rodent MND models. We are hopeful that in the coming years we may be able to progress several new drugs into clinical trials to assess their potential impact on MND progression.