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 ALS-205 (PMX205), was developed at The University of Queensland which blocks C5aR. ALS-205 is a potent antagonist of the human C5a1 receptor with no activity at the C5a2 receptor. ALS-205 has shown similar effects on other cell types including lymphocytes, monocytes and monocyte-derived macrophages. It is also highly receptor selective. ALS-205 is chemically stable to peptidase degradation in blood and gastric fluids and is both small enough and sufficiently lipophilic to be orally active at ≤1 mg/kg/day in vivo and readily accesses the brain.
In preclinical studies, Alsonex Pty Ltd has shown that ALS-205 can slow down the disease in animals and is safe to use.
The Phase 1 trial tested the safety of ALS-205. It was a randomised, double-blind, placebo-controlled, phase 1 study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple ascending doses of ALS-205 in healthy volunteers. This study was run by a small pharmaceutical company, Alsonex, who have co-developed ALS-205 with Trent Woodruff.
The study planned to enrol a maximum of 54 healthy volunteers (30 in the Single Ascending Dose (SAD) phase and 24 in the Multiple Ascending Dose (MAD) phase of this study).
The purpose of this research was to determine if ALS-205 is safe, if it affects the body as expected, and how much is in the blood after dosing. ALS-205 will be injected under the skin in the top part of the abdomen.
Plans are currently underway for a Phase 2 trial of ALS-205.
A possible treatment resulting from this study is years away. Only the Phase 1 trial has been completed in healthy volunteers to validate the drug’s safety and identify the best dosing options. It is not until successful Phase 2 and 3 trials have been completed that we will know the drug's true potential as a treatment.