Can gene editing stop ALS? Toronto’s Specific Biologics advances therapy that could help some with fatal disease

David Edgell’s childhood love of science fiction and Lego inspired him to pursue cutting-edge science when he grew up. Starting in the 2000s, the Western University biochemistry professor developed a gene-editing technique that could treat people with devastating hereditary diseases.

Now a Toronto company putting his technology to work is emerging as a budding star of Canada’s biotechnology sector.

Specific Biologics Inc. is seeking to treat people with dozens of neurological and neuromuscular diseases known as repeat expansion disorders, which are caused by a similar genetic defect. Its first target is amyotrophic lateral sclerosis (ALS), the fatal condition known as Lou Gehrig’s disease.

If the treatment works in humans, as it has in petri dishes and mice, Specific believes it could stop the progression of ALS in the one in 10 patients whose condition is caused by the defect. (About 1,000 people are diagnosed with ALS in Canada annually.) The ultimate goal is to treat people with the disorder early enough “so they never become symptomatic,” said Specific chief executive officer Brent Stead, who studied in the same lab as Dr. Edgell at Western and later convinced him to let the company commercialize his technology.

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If successful, the technology, called Dualase, could be applied to other repeat conditions, such as a variant of Huntington’s disease, and more broadly to genetic diseases including cystic fibrosis, Mr. Stead said.

Specific has pulled in a who’s who from Canada’s biotech sector to help. Its board includes industry heavyweights Paul Hastings, former CEO of B.C. biotech pioneer QLT Inc., and serial entrepreneur Richard Glickman. It has recruited U.S.-based Canadian gene-editing veterans Brad Geddes and Paul Alloway to its senior management team. “This technology could revolutionize the way people are treated with these disorders,” said Mr. Hastings. “The reward, if it works here, will be spectacular.”

On Monday, Specific will announce it has closed a US$35-million venture capital round led by North Carolina-based Hatteras Venture Partners. But Canadians still own a vast majority of the company, including early backers Lumira Ventures and adMare BioInnovations, plus Genesys Capital, BDC Life Sciences Venture Fund and Seido Capital. That degree of Canadian ownership is rare at this stage for a promising domestic biotech company, said Lumira partner Nikhil Thatte.

Dr. Edgell grew up in Victoria, obsessed with Star Trek and the novels of science-fiction writers William Gibson and Philip K. Dick. He decided to study ancient history before changing his mind and enrolling in a kinesiology program at the University of Victoria. It wasn’t scientific enough for him, so he switched to molecular biology. That brought him closer to the scientific vanguard that had long intrigued him.

As his academic career progressed, he studied so-called “junk DNA,” parts of deoxyribonucleic acid – the hereditary, twisted ladder-shaped biological blueprints inside the cells of life forms – that appeared to serve no purpose. He eventually focused on gene editing after arriving at Western in London, Ont., in 2003. (Genes are sequences of subunits within DNA that instruct cells to make proteins.)

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The field of genetic editing, in which scientists change targeted genetic material within DNA, dates back decades. Scientists Jennifer Doudna and Emmanuelle Charpentier transformed the space in 2012 by demonstrating a new process called CRISPR/Cas9, later winning the Nobel Prize in chemistry.

CRISPR is a molecular, scissors-like tool that destroys a single mutated gene on strands of DNA, then instructs the body’s cells to fix it. It was simpler, faster and cheaper than prior technologies and led to some clinical successes, including sickle-cell anemia treatment Casgevy. Health Canada in 2024 approved the sale of the gene therapy, which was developed by Vertex Pharmaceuticals Inc. and CRISPR Therapeutics AG.

But CRISPR technology has its limits. Many treatments can have “off-target” effects, destroying the wrong part of the DNA, causing serious consequences. That has irked investors. “Gene editing is virtually unfundable in the U.S.,” Lumira’s Mr. Thatte said. But “Specific has delivered every time” on its scientific milestones, he added.

Unlike other gene editors, Specific goes after problems that can’t be fixed by a single gene cut. DNA contains sections of repeated sequences which serve genetic functions. But in people with repeat expansion disorders, those sequences repeat and repeat out of control. That creates increasingly long strands within DNA, which cause toxic effects. Fixing the problem requires not one edit, but two.

Its solution is to deploy the molecular equivalent of two pairs of scissors coded into a protein. Specific packages the technology into the shell of a non-toxic virus that will be injected into the spine, travel to the brain and target neuron cells where the problem lies.

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The treatment is programmed to latch onto the specific point in the DNA where the trouble starts, as well as the other end of the out-of-control repeated sequence. It slices both ends, removes the problematic section, then fuses together the cut ends of the DNA – “like molecular Lego,” Dr. Edgell said. That leaves healthy DNA with normal repeat sequences.

The solution will require a single injection and has had no off-target effects, Specific has confirmed in preclinical studies of human cell samples and mice. It hopes to launch its first human studies in ALS patients in 2028. “There’s a straightforward, cost-effective path to demonstrating feasibility of whether or not this platform can work,” said Hatteras partner Ben Scruggs. Specific is also in talks with a pharmaceutical giant on a development partnership deal, Mr. Stead said.

For the 56-year-old Dr. Edgell, Specific’s progress and fundraising success offer some satisfaction as his family struggles with its own health struggles. He has a child with an autoimmune condition called ANCA vasculitis where the body attacks its own blood vessels. While there are treatments, they haven’t worked on his child, who was recently hospitalized with related complications.

Dr. Edgell, a scientific adviser to Specific, admits that if his child had a monogenic disorder – a condition caused by a mutation in a single gene – he’d be pushing for the company to look into the condition. “But cell gene therapy isn’t going to work here, at least not now,” he said.