Dr. Jack Jhamandas brings up a video on a computer screen in his lab at the University of Alberta’s Heritage Medical Research Centre. It shows a recorded video of a mouse easily navigating its way through a pool of water to a platform where there’s a button for it to push.
The task should be harder for the mouse, which has been genetically engineered to have Alzheimer’s. During an earlier test, it struggled to make its way to that button. Then it was administered a drug that Jhamandas and his team of researchers have been developing for decades, and it found its way again — a memory seemingly restored.
While it’s in early stages, that drug appears to do something that no other on the market has done successfully: potentially preventing Alzheimer’s symptoms and even reversing the damage. So far, it’s working. At least in mice.
Attempts to bring new drugs to market can take years and cost billions. Sometimes, those attempts ultimately fail. But Jhamandas, now 73 and putting off retirement to find a treatment for a disease that is the most common cause of dementia in Canada, believes there’s reason for hope. And he’s become surrounded by others who believe that too, and who are eager to help.
During his post-doctorate in the late 1980s, Jhamandas and his team focused on an area of the brain called the basal forebrain. He was initially interested in the role it plays in regulating blood pressure. But when he learned that the area was even more critical for learning, and often the first area of the brain to be affected by Alzheimer’s, those facts stood out, partly because of what he was seeing in the clinic.
Formerly a practicing medical doctor, Jhamandas had known many patients who were scared by the confusion associated with the early days of the disease. “I saw firsthand the helplessness, and also felt it,” he says. The only drugs available to prescribe were stopgap measures that only temporarily improved symptoms. Sometimes they did nothing at all.
He felt motivated to learn more, shifting his focus so entirely that studying Alzheimer’s disease became a full-time occupation.
He was in good company. When Jhamandas started his research, a cottage industry was forming in the medical community. For a long time, researchers have known that those with diabetes are much more likely to get dementia. Common to both conditions is a rogue protein called amyloid that can negatively affect a variety of vital functions in the body. In the brain, amyloid acts like a wrecking ball, disrupting communication between neurons, and further knocking out memories while impairing cognition.
Many other scientists with magnitudes more resources had also tried but failed to stop amyloid. A trial vaccine in the early 2000s helped the body develop antibodies against it but sometimes also caused major inflammation, causing the drug to be shelved. Next came genetically engineered or chemically synthesized antibodies. While these improved cognition for those with early signs of Alzheimer’s, occasional, irreversible side effects such as brain swellings made these treatments too risky as well. Researchers also tried to stop amyloid from forming in the first place.
Over the years, several drugs have been released that can temporarily improve cognitive function by boosting levels of the acetylcholine, a chemical that helps transmit signals between nerve cells, and is often depleted in Alzheimer’s patients. These therapies alleviate symptoms, but don’t stop them. And there are diminishing returns. The further the disease progresses, says Jhamandas, the less effective those drugs become.
Today, his work tests the hypothesis that drugs developed for blocking amylin — which influences blood glucose levels for diabetes patients — might also protect the brain from amyloid.
Jhamandas is optimistic. The first real breakthrough, he says, happened recently; several therapies can in fact remove that rogue protein from the body.
Jhamandas saw positive results quickly. His team started by testing two drugs already effective in treating diabetes, applying them first to mouse brain cells in a Petri dish, then to mouse brain slices, and eventually to live mice. The drugs, it turned out, were protecting the brain cells from death or destruction caused by amyloid. And the work began to attract attention.
Though not from everyone. Jhamandas met with eight pharmaceutical companies to potentially partner with, but they were wary of the nature of the drugs being peptides, or chains of amino acids, the building blocks of proteins. These can be barred by the blood-brain barrier, a kind of filter built into blood vessels that protects the brain. Those peptides can also be degraded by enzymes in the blood, and, in general, are extremely expensive to make. The other challenge was that the end product was likely in a needle — a potential marketing nightmare.
Then, eight years ago, Jhamandas was giving a lecture attended by Dr. Lorne Tyrrell, founding director of the Li Ka Shing Institute of Virology at the University of Alberta. The institute uses artificial intelligence for drug design led by top scientists and global collaborations. And, conveniently, it’s located near Jhamandas’ lab.
Tyrrell immediately wanted to partner with Jhamandas. “There’s been a few times in my career where I saw certain results that really said: ‘This is different,’” says Tyrrell. It gave him the same visceral feeling he had experienced years prior, when he sensed he was on the brink of something big. That thing was Lamivudine, the first oral antiviral agent to treat chronic hepatitis B. Pharmaceutical and biotechnology giant GlaxoSmithKline has sold around 11 billion doses of that medication since it was released in 1998.
As part of the partnership, Jhamandas gained access to the Li Ka Shing commercialization hub and computational drug discovery platform, which hosts a slate of AI-powered supercomputers that create the formulations that can lead to actual medications. Using that technology, the team screened seven million compounds (created by a team of in-house medicinal chemists) in just three weeks. “This is a very demanding area, requiring the involvement of many specialist drug developers, particularly as these drugs need to cross the blood-brain barrier,” says Sir Michael Houghton, director of the Li Ka Shing Applied Virology Institute and 2020 Nobel Prize winner.
Along the way, Jhamandas has drawn increased funding from multiple sources and formed additional partnerships, such as with Applied Pharmaceutical Innovations, a local, not-for-profit organization that can help them develop a drug for market. Though he acknowledges that his team is not as well positioned as the multinational pharmaceutical companies, Jhamandas believes they will move their agenda forward. “The end game,” he says, “is to develop a partnership with Big Pharma so you can move this quickly for patients and their families.”
Identifying and launching a treatment for any health condition, let alone Alzheimer’s, is a lengthy process. But persistence can pay off. Jhamandas and his team now realize that their original drug formulations may actually be brought to market. Over the next few years, their work will be subjected to toxicity studies and several phases of trials before approvals by Health Canada. But there’s potential for either an injection, pill or possibly both to become prescribed treatments.
While Jhamandas is persistent, being patient may be more challenging. He feels a sense of urgency to keep moving before age and all its related complications catch up to him. Though he could pass for a decade younger and still moves around the lab with ease, it’s not lost on him that he’s increasingly at risk for the very disease he’s spent his life’s work trying to cure.
“There are no guarantees in science or life. But I want to know we gave it our very best and spared no effort,” he says. “If I don’t get to sit on a beach for a few more years, it’s worth it.”
This article appears in the May 2025 issue of Edify
