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.
For the Phase 1b trial, the primary objective is to evaluate the safety and tolerability of a single dose of PMX205 in individuals with ALS. The secondary objectives are: to determine the plasma pharmacokinetics (PK) of PMX205, evaluate PMX205 levels in the cerebrospinal fluid (CSF) after dosing at a single level, and to evaluate PMX205 pharmacodynamic (PD) activity by measuring cytokine levels following C5a challenge in peripheral immune cells. It is important to determine the extent to which PMX205 crosses the blood-brain barrier and enters brain tissue in individuals with ALS
PMX205 is to be administered as a subcutaneous (SC) injection into the anterior abdomen. Patients who have ALS or are likely to have ALS will be selected by the investigators based on history, examination, imaging and laboratory results. A total of up to 8 participants will be enrolled and assessed for safety (physical exam and clinical laboratory pathology), PMX205 PK and PMX205 PD during the study.
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.
Wesley Medical Research, The Wesley Hospital
A/Prof Robert Henderson +617 3193 3387