Updated October 20, 2017

Very early in his medical training, Dr. Lawrence Korngut was introduced to the concept of ALS. “As a neurologist, I have always been very interested in the physical exam and ALS is the perfect example since the diagnosis is made entirely by physical exam,” said Dr. Korngut in an interview with ALS Canada. “I am continuously inspired by people living with ALS and their families. ALS is a disease of weakness, but these are the strongest people I know.”

Dr. Korngut moved to Calgary in 2007 where he has continued a relentless pursuit to find new treatments and interventions to help people living with ALS. He is a neurologist and clinical neurophysiologist at the Calgary Neuromuscular Clinic and the Director of the Calgary ALS and Motor Neuron Disease Clinic.

The Pimozide Potential

The discovery that the drug pimozide might have an impact on slowing disease progression began with worms in a Petri dish on the lab bench of Dr. Alex Parker, a researcher at the University of Montreal. Dr. Parker genetically engineered worms with a human form of ALS and tested them with a battery of drugs to look for a positive impact on motor neuron (health and function. He found a bunch of antipsychotic drugs that would work, but pimozide seemed to be the most effective. He shared his results with other researchers who then explored pimozide in other animal models.

At the 2012 ALS Canada Research Forum, Dr. Korngut heard Dr. Gary Armstrong present his positive findings about pimozide in zebrafish that had been altered with a human form of ALS. A postdoctoral student at the time, Dr. Armstrong had been working with lead researcher Dr. Pierre Drapeau at the University of Montreal. Dr. Korngut thought the next step would be to translate this preclinical research. “I thought, since pimozide is already an approved drug that we know a lot about, is available, and costs about $0.09 per pill, a clinical trial in human volunteers seemed like the next logical step,” he said.

Pimozide is an older drug, typically used to treat schizophrenia. “It was used at high doses and had some notable side effects, so it has mostly been replaced with newer generation drugs today,” Dr. Korngut explained. “We don’t know exactly how pimozide works, but the evidence so far suggests that it strengthens the electrical connections between nerves and muscles, allowing them to function better,” he continued. “In animal models, there seemed to be some promising signs of effect on the disease, but we don’t know yet if the drug will work the same way in humans.”

Translating Preclinical to Clinical Research

Since 2013, Dr. Korngut has been leading a ground-breaking, first-in-human clinical trial for pimozide at the University of Calgary among 25 volunteers with ALS. He is investigating whether the drug can slow disease progression and exploring how much medication needs to be taken to have an effect. The trial opened in April 2015 and is now complete. The Quirk Family in Calgary and the University of Calgary provided funding support, which is noteworthy since trials for existing, inexpensive drugs are not usually of interest to large pharmaceutical companies.

While the small number of study participants makes it impossible to draw any concrete conclusions, the results are promising. “We found the dose that is most likely to be best tolerated among people with ALS, a lower dose than is used in other conditions and we have some preliminary evidence that pimozide is helpful.” said Dr. Korngut. “At this point, though, people with ALS should not use the drug yet until we study it further in a larger number of volunteers as we don’t know that it is helpful but we know that it is associated with significant side effects.”

Plans for a larger scale trial are already established. After getting the first trial started, Dr. Korngut collaborated with Dr. Lorne Zinman at the University of Toronto. They applied to ALS Canada for funding and were successful in securing an ALS Canada – Brain Canada Arthur J. Hudson Translational Team Grant in 2015, a total of $489,857, to support the study. Health Canada and the ethics committee at the University of Calgary are currently reviewing the clinical trial protocol that will test pimozide in 100 volunteers with ALS in eight clinics across Canada. If the proposal is approved, Dr. Korngut and his colleagues would be able to begin recruiting patients, possibly as soon as autumn 2017.

“There is a lot of reason to be optimistic about the research going on in the ALS community right now. That’s a testament to all the people with ALS and their loved ones who volunteer in clinical trials as well as the donors, patient organizations and dedicated researchers,” said Dr. Korngut. “The pimozide story is a great example of a treatment identified through very fundamental research that is being explored in human clinical trials because of funding by ALS Canada and Brain Canada. Without their contribution, this research would not be happening.”

ALS Canada Virtual Research Forum

Update: Dr. Korngut was one of more than 20 speakers who participated in the ALS Canada Virtual Research Forum in August. You can listen to his full presentation online here.

Posted in: Research