Queen’s researchers working on gene therapy answer to rare, fatal genetic disorder

Dr. Jagdeep Walia is a medical geneticist and full-time professor in the division of medical genetics in the department of pediatrics at Queen’s University. Soon after joining Queen’s in 2012, Walia launched a genetic research program that focuses on developing gene therapies for inherited and acquired neurodegenerative disorders.

His research recently received a $5 million contribution from the Hilary and Galen Weston Foundation.

Walia is looking closely at GM2 gangliosidoses, a group of three related genetic disorders that cause the progressive deterioration of nerve cells called Tay-Sachs disease, Sandhoff disease, and AB variant. These disorders can be diagnosed in infants, juveniles and adults, but Walia’s current research is first investigating gene therapies to treat babies diagnosed with the rare disorders.

He will expand into investigating therapies for the juvenile and adult onset for these disorders later.

GM2 gangliosidoses is a type of brain lipid that is missing an enzyme, which can then metabolize, Walia explained.

“When that happens that brain lipid accumulates in brain cells. It’s not good for the brain cells, and they start dying. In the infantile form, children (usually) are dying by the age of four years old.”

Walia said that the children diagnosed are often born healthy, but by the time they are four to seven months old, are showing signs of a loss of development. Approximately one in 200,000 babies born in Canada will be diagnosed with the disease.

“Either they’ve stopped developing or they start losing milestones,” he said. “For example, if they’ve started sitting, then they (can no longer sit) because brain cells have started dying.”

The loss of motor function eventually leads to a vegetative state, Walia said.

“They don’t speak, their hearing is impaired, they slowly can’t see. It affects many neurological parts.”

The funding from the Hilary and Galen Weston Foundation will facilitate a clinical trial that Walia hopes to launch in early 2027.

“We got funding to say, ‘Your work seems reasonable, now take it to the next stage,’” Walia said. “We also got some funding from (the Canadian Institutes of Health Research) for the same project, so we have about $8 million right now, and that’s what we’re using for the clinical trial for GM2 gangliosidoses, which is going to start sometime early next year.”

The genetic defect that causes these disorders has been understood for a long time, Walia said.

“The disease has been there for many decades, and there was no treatment,” he said.

Walia and his research team are pursuing gene therapies that they have developed in their lab at Queen’s that are showing promising signs.

“Gene therapy has started to give a hope to these patients,” he said. “This might be a treatment to alter their lives. It may improve symptoms, or stop them from happening. It may reverse the condition a little bit. But we don’t know yet how much it can do.”

Walia’s lab is one of only two or three groups in the world looking to cure these genetic disorders.

“We can tell by our animal studies, that some animals who were treated in some doses were basically cured,” he said. “But there is a transition between animals to humans, and we still have to see what dose and what effect will happen in humans.”

The mechanics of gene therapy are complicated, and broad.

“You can replace a defective gene by different methods,” Walia said. “The ultimate goal is that the protein which is not getting made, gets made. Or, if it’s getting over-made, how can it be reduced?”

One is called gene addition, and the other gene editing. A third approach is called gene silencing.

“You need to choose the right vector, you need to target it to the right cells, and you have to have a right dose, so that it can reach a minimum threshold number of cells, so that the disease can be corrected.”

Walia became deeply interested in gene therapies in and genetic research early in his education. Currently, he’s working on research for nine different conditions.

“I came to Canada with a dream to work on gene therapies,” he said. “That’s what I’ve been trained in for my post-doctorate, and I always wanted to do research on brain-related conditions.”

Walia feels that his work is a way to contribute to society.

“You are doing something for patients where there is no treatment and there is a desperate need,” he said. “So you’re contributing to the field, and if you will be successful, probably you will give a treatment for patients in need.”

He’s witnessed the impacts of fatal genetic disorders in patients.

“I’ve seen four or five patients already with this condition, but I could not do anything for them,” he said. “But we have already used (this gene therapy) in three humans, and there will be more coming next year.”

Patients will be participating from all over Canada and the United States.

Walia wants to bring hope to people through his work.

“They may have this feeling that for rare disorders, there’s nobody there to support them,” he said. “I would say yes, there are researchers who are working for them. There are foundations who understand their pain and their desperate need, and they are putting money towards those research efforts.”

Walia also wants the public to understand the great expense associated with rare disorders and the research that goes into them.

“We definitely need more and more support,” he said. “No government funding agency can singly afford rare disease research, which is very very expensive, and the industry is not very interested because these are diseases that most likely will not get commercialized. They’re not of commercial interest, because there may be less profit.”

Walia expressed thanks to the foundation for their gift.

“They saw the need for these patients,” he said.