RARE Daily

Scientists Create First Mouse Model for 4H Leukodystrophy

September 13, 2023

Rare Daily Staff

A research team has succeeded in creating the first representative animal model of 4H leukodystrophy, a milestone in research into the deadly neurodegenerative diseases known as leukodystrophies.

Leukodystrophies affect the myelin, the insulating sheath that surrounds and protects the brain cells or neurons and contributes to cell-to-cell communication. 4H leukodystrophy is the combination of myelin deficiency leading to motor, balance, and coordination problems, as well as a deterioration in children’s physical condition) and two other conditions: dental anomalies and endocrine dysfunction leading to delayed, arrested or absent puberty.

The team, led by Geneviève Bernard at the Research Institute of the McGill University Health Centre, published a study of their work in the Journal Brain. They said the model will help to shed light on how the mutation affects the body and advance the search for treatments.

The researchers have succeeded in recreating a POLR3B mutation in a mouse model. POLR3B mutations cause around half of all cases of 4H leukodystrophy. The model displays the main features associated with the disease phenotype, as seen in patients: hypomyelination, hypodontia, and craniofacial anomalies.

“This significant progress will allow us to understand the disease better and to test putative therapies, which we have already started doing,” said Bernard, a scientist in the Child Health and Human Development Program at the RI-MUHC and a neurologist at the Montreal Children’s Hospital of the MUHC. “Without such a disease model, there would be limited to no hope of finding a cure for this disease.”

The research was funded by the Yaya Foundation for 4H Leukodystrophy, the Montreal Children’s Hospital Foundation, donations from the Tallman family, and Leuco-Action, in addition to being supported by the Fonds de Recherche du Québec—Santé (FRQS) and the Canadian Institutes of Health Research.

“This discovery is a critical building block in the quest to discover effective treatments for people affected by 4H and demonstrates the advances that are possible when patients, families, and researchers come together to identify the most important problems to solve and find the right people to solve them,” said Ron Garber, co-founder and board president of the Yaya Foundation. “This collaboration and the discoveries it has already produced give our community hope that people affected by 4H will one day soon be able to live longer, fuller lives.”

Photo: Geneviève Bernard and Xavier, who suffers from 4H leukodystrophy

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