Study on new ALS treatment encouraging

Daniel Rompré says he’s not looking for a miracle to reverse damage done by ALS, but he’s hoping a new drug may help stave off further decline.

A former construction worker at both of Montreal’s superhospitals, Rompré, 47, has a deadly neurodegenerative disease for which there is no effective treatment.

So when his doctor asked him if he’d like to be part of a national study using a repurposed medication, he didn’t hesitate.

“Obviously, I said yes,” Rompré said. The statistics in this illness are not good, he added, as 90 per cent die within three years. “I’m looking for a way to live.” Rompré will be enrolled in a clinical trial using pimozide, an antipsychotic drug to treat schizophrenia. Diagnosed with ALS in March 2016, the father of two girls can no longer use his left arm, his upper body muscles are weaker and he has trouble speaking.

Two years ago, pimozide slowed the progression of amyotrophic lateral sclerosis in animal models with the disease — worms, zebrafish and mice — and then in a modest study of 25 volunteers with ALS.

Patients who took the drug for six weeks seemed “to stabilize” their symptoms. Published in JCI Insight journal this week, the pilot study led by scientists at the Université de Montréal and University of Calgary medical school concluded that a small dose of pimozide was safe over the short term.

ALS affects about 3,000 Canadians and 100,000 individuals worldwide. The disease attacks neurons and the spinal cord and causes progressive paralysis of the body.

Patients typically lose the ability to move, speak, swallow and breathe. The average survival rate is two to five years from diagnosis.

In May, the U.S. Food and Drug Administration (FDA) approved the first new treatment in 22 years after the drug edaravone slowed the progression of the disease in a small Japanese study.

Initially developed to treat stroke patients, edaravone is not approved in Canada. The current medication, riluzole, does little to prolong life, and that has led to a spate of testing of existing medications.

It took about five years and nearly 4,000 drugs before scientists at the Université de Montréal research centre narrowed their target down to a group of antipsychotic drugs, and then to one in particular — pimozide.

The drug seemed to maintain the connection between motor neurons and muscles in worms, zebrafish and mice that were genetically modified to exhibit a form of ALS, explained Alex Parker, a CRCHUM researcher and professor at Université de Montréal. It’s too soon to draw conclusions, he said, but when tested with human volunteers over six weeks, it seemed to stabilize the disease in the short term.

The next step is Phase II clinical trials with about 100 patients like Rompré to test the drug over six months for safety and efficacy. At Phase III, a drug can be sent to Health Canada for approval.

Pimozide is “an exciting, landmark Canadian-only trial of this magnitude, 100 patients at nine centres across Canada,” said David Taylor, vice-president research, ALS Canada, which is funding the trial along with Brain Canada.

However, there are several therapies in late-stage trials that may put a dent in the disease, he said, and pimozide is on par with other drugs. For example, international results for a drug called tirasemtiv, developed by Cytokinetics, which seems to work on making muscles more responsive, are expected within a few weeks, Taylor said.

Also in Phase III is masitinib by the French company Biotech AB Science, which seems to reduce immune and inflammatory effects of ALS, and a stem cell therapy by the Israeli company BrainStorm that seems to have a protective effect on neurons.

“We’re cautiously optimistic,” Taylor said. “We’re always very cautious when it comes to interpreting too much. With ALS, you really don’t want to cause false hope.”