In Prof. Alexey Pshezhetsky’s lab, relentless work on several fronts is bringing us closer to a therapy for Sanfilippo Syndrome—a rare but debilitating disease that gradually robs children of their physical and cognitive abilities before taking their lives far too soon.
A giant step has recently been taken in our race against Sanfilippo Syndrome and should help accelerate the development of much-needed treatments. A team led by CHU Sainte-Justine researcher and Universite de Montreal professor Alexey Pshezhetsky was able to resolve the structure of HGSNAT: the enzyme whose deficiency causes one of the subtypes of the disease. Together with a team at Shanghai University, they used an advanced imaging technique to gain groundbreaking insights into how HGSNAT functions. This information will be extremely valuable in developing an effective treatment for the disease.
A Complex and Devastating Disease
Sanfilippo Syndrome is a rare genetic disorder that causes a toxic build-up in the brain cells, leading to progressive damage to the central nervous system.
“It is a terrible condition. You watch your child deteriorate, and there’s nothing you can do to stop it. It’s like Alzheimer’s disease in a 10-Year-Old.”
There are four types (A, B, C, D) of the Sanfilippo Syndrome, each the result of a mutation in a different gene but sharing symptoms such as developmental regression, intellectual disability, and behavioural problems. Sanfilippo syndrome belongs to the groups of childhood dementias which together affect thousands of children in Canada.
All types of Sanfilippo disease are incurable and fatal, with life typically ending before adulthood. In the face of so much suffering, the status quo is simply not an option. Prof. Alexey Pshezhetsky’s team is working tirelessly to grow beyond current solutions offered to patients.
Combining Efforts on Multiple Fronts
Supported by a family who lost their daughter to Sanfilippo Syndrome, the Elisa Linton Sanfilippo Research Laboratory is exploring several promising approaches, including one called “chaperone therapy”. This is where the new knowledge about the HGSNAT is so important.
In children with Sanfilippo syndrome type C, this essential enzyme is either absent or not functioning properly. As a result, a toxic buildup occurs, leading to the death of brain cells and neurological decline.
The good news? In almost half of Sanfilippo type C children, the problematic HGSNAT are still partially functional, offering a chance to “fix” them with drugs called chaperones.
“Chaperones act as helpers, guiding enzymes to get a correct structure and function properly. With Professor Christopher Cairo at the University of Alberta, we’re testing different chaperones and have received funding from the Canadian Glycomics Network to intensify this work.”
—Alexey Pshezhetsky
As part of another collaboration, the team is also investigating transplantation of gene-corrected blood stem cells, a remarkably effective method that is already widely used for other conditions such as leukemia. With this approach, the patient’s stem cells are taken, repaired and re-injected to make healthy blood cells that produce the fully functional enzyme.
“This procedure could cure very young, symptom-free children and newborns who are diagnosed early. For them, one treatment would last a lifetime. For older kids, it could provide partial relief and stabilize the disease. In about two years, we should be ready to save lives.”
However, a key challenge remains with this therapy: finding ways to detect the disease earlier. Children with Sanfilippo Syndrome are born with it, but most don’t show symptoms until between the ages of 2 and 6.
The Promise of Combined Therapies
Prof. Alexey Pshezhetsky, along with the medical and scientific communities, believes that combining therapies holds a great promise for treating Sanfilippo Syndrome. Together with a research team at SickKids Hospital in Toronto, Professor Pshezhetsky has received a grant to test a combination therapy that integrates his gene-corrected cell approach with a treatment developed at SickKids.
“While Sanfilippo affects one in 24,000 births, our research could also have a direct impact on related genetic disorders, which collectively affect one in 5,000 children.”
—Alexey Pshezhetsky
In Tribute to Elisa Linton
A world-renowned expert who has helped unlock new ways to understand and treat lysosomal disorders—serious pediatric conditions such as Sanfilippo Syndrome—Prof. Alexey Pshezhetsky has a long history with the Linton family, who, more than 20 years ago, founded The Sanfilippo Children’s Research Foundation for their daughter Elisa and others like her.
Elisa lived to the age of 22, but sadly Sanfilippo Syndrome took her life in 2016. Her legacy lives on, giving hope to other patients facing this heartbreaking diagnosis.
“This is so encouraging to know that our precious daughter’s legacy with Sanfilippo research continues in such a magnificent and meaningful way. We appreciate seeing that our philanthropic investment is so close to making a significant difference in the lives of children and families with this horrific disease.”
“Each discovery brings us closer to our goal. Donors like the Lintons are essential—they allow us to move forward, faster. And with this disease, every moment counts.”
–Alexey Pshezhetsky
Your generosity has a profound impact, reaching families across Canada and around the world. Thank you for supporting research at Sainte-Justine and helping to give children like Elisa a future.
