Anti-inflammatory drug could slow motor neuron disease

University of Queensland (UQ) researchers have shown that the anti-inflammatory drug PMX205 is effective in animals with amyotrophic lateral sclerosis (ALS), in a breakthrough which could see the drug taken to human trials as early as 2019.

There is no known cure for ALS, a form of motor neuron disease (MND), with an average life expectancy of two and a half years following diagnosis. As noted by UQ’s Dr John Lee, the only drug currently available for patients prolongs survival by two to three months at most.

“The complement system is up-regulated in ALS, with recent studies indicating that the activation product C5a accelerates disease progression via the C5a₁ receptor (C5aR1),” the UQ researchers wrote in the British Journal of Pharmacology. They decided to examine the therapeutic effect of a C5a₁ receptor antagonist, PMX205, in mice — with promising results.

“Mice treated with PMX205 before disease onset had significantly improved hindlimb grip strength, slower disease progression and extended survival, compared with vehicle treatment,” the researchers wrote.

“PMX205 treatment beginning 3 weeks following disease onset also attenuated disease progression, significantly extending survival.”

Dr Lee said PMX205 could help manage patient symptoms to improve quality and length of life. “In animal models, PMX205 made a visible difference to tremors, muscle strength and mobility,” he said, “and if this is reflected in people, it could make a real difference to patients.”

The research team was led by Associate Professor Trent Woodruff, who will now test the drug in a range of MND models. His team’s next project will focus on sporadic MND, which accounts for 90% of patients.

“To date we have only tested the drug in one model based on the inherited form of MND, but we believe the same inflammatory pathway is likely to be active in all forms of MND,” Associate Professor Woodruff said.

The drug has now obtained orphan drug approval from United States and European licensing authorities, which allows for accelerated progression to human trials. A private company will undertake preclinical safety trials in the near future, said Associate Professor Woodruff.