The European Medicines Agency (EMA) explains that monepantel is an anthelmintic therapy, or a type of therapy that is used to expel worm-like parasites called helminths or nematodes from the gut. Says the EMA:

Monepantel blocks part of the receptor, the nicotinic acethylcholine receptor, that is specific to the nematodes. This causes paralysis and death of the worms.

A Phase 1 Study: Repurposing Monepantel for ALS

12 individuals enrolled in the Phase 1 MEND clinical trial. Once enrolled, the participants were split into two cohorts. The first cohort received 2mg/kg/day and 6mg/kg/day doses of orally administered monepantel, with the second cohort receiving 4mg/kg/day and 10mg/kg/day doses. Through the study, researchers wanted to learn:

• The pharmacokinetics of oral monepantel
• How safe this therapy was in this population
• Whether monepantel was well-tolerated by participants

In terms of safety and tolerability, monepantel was both safe and well-tolerated. No patients discontinued from the study due to adverse reactions. Additionally, no deaths or dose-limiting toxicities occurred. While some adverse reactions happened during the course of the study, only an extremely small percentage were linked to monepantel.

Other findings from the trial include:

• Patient physical function, which includes speech, dressing, swallowing, and breathing (among other measures), remained relatively similar at the start of the trial when compared to the end of the trial. Researchers believe this shows that monepantel slowed ALS progression.
• Using external data from 30 matched controls within the PRO-ACT database, researchers found that disease progression was slowed by 39% through both cohorts. When looking at each cohort specifically, disease progression slowed by 23% in the first cohort and 58% in the second cohort. Researchers believe that this equates to approximately 13.5 months (1 year, 1.5 months) to 56.5 months (4 years, 8.5 months) of additional survival time, which is significantly higher than the additional life expectancy granted by current therapies.
• People treated with monepantel saw higher concentrations of monepantel’s metabolite in the cerebrospinal fluid (CSF) and lower levels of neurofilament light chain.

After 10-16 months of daily monepantel treatment, patients were given the opportunity to enroll in an open-label extension study. Additionally, researchers identified the ideal study dose for future clinical trials.

Understanding ALS

Amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease, is a progressive neurodegenerative disorder that causes nerve cell death in the brain and spinal cord. ALS exists under the umbrella of motor neuron diseases, which are conditions characterized by motor neuron deterioration and death. Motor neurons are responsible for voluntary muscle control. When these neurons degenerate and die, people gradually lose the ability to move their muscles. The exact cause of ALS is not fully understood. Many believe that ALS development hinges on a combination of environmental and genetic factors. Symptoms of amyotrophic lateral sclerosis often begin with muscle weakness and stiffness, frequent tripping or falling, clumsiness, and difficulty walking or performing small movements. As ALS progresses, people may experience difficulty speaking and swallowing, slow or slurred speech, poor posture, and muscle twitching. Some people may also experience psychological distress. There is no cure for ALS, though treatments can aid in improving quality-of-life and symptom management.