MONTREAL, July 12 2022 – A study conducted by the team of Dr. Alexey V. Pshezhetsky, Director of the Elisa Linton Sanfilippo Research Laboratory at the CHU Sainte-Justine Research Centre, presents a potential therapeutic approach for treating this rare genetic nerve degeneration that affects children and adolescents. The results were recently published in the prestigious scientific Journal of Experimental Medicine.

Sanfilippo disease leads to a progressive loss of physical and neurological development until premature death, often before age 15. “It’s one of the most terrible diseases because you see your child deteriorate and you can’t stop it. It’s like having Alzheimer’s at 10 years old,” says Dr. Pshezhetsky, who is also a professor at the Université de Montréal.

Repairing mutant enzymes with molecular chaperones

Most patients with Sanfilippo disease have genetic mutations that produce enzymes — a type of protein — whose three-dimensional structure does not fold correctly. With this anomaly, certain compounds that are usually eliminated or recycled by the body concentrate in the cells and cause the disease.

The existence of molecular chaperones, which promote proper folding of other proteins, has encouraged research into the treatment of rare genetic diseases. Dr. Pshezhetsky’s recent study showed that, in most cases, the mutant enzyme can be repaired by treatment with molecular chaperones.

In mouse models with this enzyme defect, memory loss and most pathological changes could be improved or even blocked by daily doses of a chaperone: oral glucosamine.

According to Dr. Pshezhetsky, “these results demonstrate that chaperone therapy can be an effective treatment for Sanfilippo disease, particularly for patients with mutations that cause enzyme misfolding. Unfortunately, the concentrations of glucosamine that we administered to mice are dangerous for humans. Therefore, we need to identify more potent chaperones to reduce the drug doses to be administered, while maintaining the effectiveness of the therapy.” 

Dr. Pshezhetsky’s team is currently working with researchers at the University of Alberta to develop more potent drugs based on the glucosamine molecule. This research is supported by a team grant from the Canadian Glycomics Network (Glyconet).

In Quebec, CHU Sainte-Justine is responsible for diagnosing and treating nearly 70% of rare disease cases. It is a world leader in contributing to the advancement of knowledge and the development of new therapeutic approaches for the prevention, diagnosis and treatment of these diseases, particularly in pediatrics.

Warning

As mentioned above, in this study, the concentrations of glucosamine administered to mice are dangerous for humans. Under no circumstances should a person with the disease take over-the-counter glucosamine products without consulting a physician.

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