A team from the McGill University Health Centre Research Institute has developed the first representative animal model of 4H leukodystrophy, a common form of the fatal and currently incurable neurodegenerative disease that affects around one in every 4,700 children.

The model should help researchers better understand leukodystrophies and enable them to test different therapies.

"We absolutely needed an animal model to help develop therapies," said study author Dr. Geneviève Bernard, a world authority on leukodystrophies. "And we've already started testing gene therapies.

Leukodystrophies attack myelin, a kind of "insulating sheath" that surrounds and protects brain cells or neurons and helps them communicate with each other.

The researchers successfully recreated the POLR3B mutation in mice, which causes around half of all 4H leukodystrophy cases. Bernard and her team had already identified this gene in 2011.

Diagnosed after birth, 4H leukodystrophy can lead to multiple health problems, from motor and balance disorders to puberty failure and early death.

It took years of effort and countless attempts before Bernard and her colleagues finally developed an animal model of the disease.

Until then, she said, "it was all or nothing": either the genetically modified mouse didn't get sick, or it didn't survive the pregnancy.

"We were interested in the brain [...] and it's us who decide when the [genetic] error appears," said Bernard. "This allows us to have a mouse that is sick, and also to avoid the mouse dying. And we want it to be sick so we can treat it."

While human babies are born with leukodystrophy, she explained, researchers activate the disease in mice after they're born.

These mice have already enabled researchers to begin testing different treatments, including sending a virus to correct the genetic error, which has already been successfully used to treat other health problems.

"I think this is the treatment option with the best chance of working," said Bernard.

Some fifty different types of leukodystrophy have been identified to date, but many forms of the disease remain undetermined, and around 25 per cent of families are waiting for a diagnosis.

"It's truly a privilege to care for these patients and their families," Bernard concluded. "Children are so resilient [...] We tend to always want more, more, more -- but they've got what they've got, and they deal with it. That's their life. You learn things from being around them, and you become a better person."

Collectively, rare diseases affect around three million people in Canada, and some 500,000 in Quebec.

The findings of this study were published in the medical journal Brain.

This report by The Canadian Press was first published in French on Sept. 13, 2023.