Researchers at the University of Calgary in Canada are enrolling amyotrophic lateral sclerosis (ALS) patients for a Phase 2 clinical trial to evaluate the potential therapeutics effects of a well-established antipsychotic drug called Orap (pimozide).
The research team, led by Dr. Lawrence Korngut, associate professor at the Cumming School of Medicine at UCalgary and member of the Hotchkiss Brain Institute (HBI), is conducting the trial at nine hospital centers in Canada to assess whether Orap can stabilize the disease.
The trial is partially funded by money raised from the annual ALS Ice Bucket Challenge, a viral internet fundraiser where people raise money for a cause by pouring buckets of ice water over their heads.
About 100 patients enrolled in the Phase 2 pimozide trial (NCT03272503) will be randomly assigned to receive either pimozide at 4 mg per day or a placebo. The treatment will continue for five months, and the trial outcomes will be measured at month six.
During the treatment phase of the study, patients will visit the clinic eight times and have one phone visit.
In the optional, observational second part of the trial, investigators will follow patients for up to five years after they’ve stopped treatment.
The clinical trial was set up after a study by researchers at the University of Montreal showed that Orap stopped disease progression in animal models of ALS — in worms, fish, and mice. Specifically, researchers were capable of preventing paralysis in fish with a genetic form of ALS, a known feature of human ALS.
“Pimozide has been well known for decades as a drug approved for treating certain types of psychiatric conditions like schizophrenia, and it only costs nine cents per pill,” Korngut said in a press release.
“Recent studies have shown genetic links between schizophrenia and ALS. We knew the next logical step was to test it on human volunteers — patients living with ALS,” he said.
Korngut launched an initial clinical trial with 25 ALS patients in 2015 where they “used a lower dose of pimozide than that used for other conditions, and now have preliminary proof that the lower dose may be useful in stabilizing ALS,” Korngut said.
In that study, researchers observed that after only six weeks of treatment with Orap, patients were able to retain the control of the thenar muscles – located between the thumb and index finger of the hand. Loss of control of these muscles is one of the first signs of ALS.
The mode of action of Orap in ALS patients remains unknown – whether it preserves only the normal neuromuscular function of these muscles or if it actually has a curative effect and acts on the mechanisms underlying the disease progression.
This trial will confirm the potential therapeutic effects of Orap for ALS, a disease currently without any effective treatment.
Korngut emphasizes that caution is required regarding Orap’s use, because “at this stage, people with ALS should not use this medication. We must confirm that it is useful and safe in the longer term. It is also important to be aware that pimozide is associated with significant side-effects. Therefore, it should only be prescribed in the context of a research study,” he said.