Leukodystrophies and genetically determined leukoencephalopathies are a group of rare, typically neurodegenerative genetic diseases caused by abnormalities in myelin or white matter, which is involved in protecting neurons, or nerve cells, and ensures the rapid conduction of nerve impulses.
They can be split into 2 groups: hypomyelinating (insufficient myelin deposition during development) and non-hypomyelinating (altered myelin homeostasis) leukodystrophies.
Many different kinds of leukodystrophy exist, caused by variations in different genes and although each form is individually rare, collectively leukodystrophies affect approximately 1 in 4733 live births (Soderholm et al., 2020). They primarily affect children, leading to progressive disability and death, months to years following onset.
With no available treatments and an estimated 20-30% of patients without a precise diagnosis despite extensive clinical testing, much work is still needed. Finding the cause of these diseases, the faulty gene, is the first step towards finding a cure.
We have developed a cohesive and comprehensive research program on leukodystrophies with patient participants from across the globe. With a "bedside to bench and back to bedside" approach, both our basic and clinical research teams, led by Dr. Geneviève Bernard look to make a real time impact on patients with leukodystrophy that will last into the future.
Our research program includes all leukodystrophies but have a focus on hypomyelinating leukodystrophies, specifically on one disorder called POLR3-related or 4H leukodystrophy. Children with this disease develop progressive difficulties in walking, talking, swallowing and seeing. 4H is caused by mutations (or alterations) in RNA Polymerase III (Pol III) genes which are important for the survival of cells.
Cellular models using iPSCs (induced pluripotent stem cells) for POLR3-related leukodystrophy are used to study disease pathophysiology by visualizing the disease at a molecular level. Generated from patient cells, they allow us to study the impact of specific patients' mutations in engineered brain cells.
Animal models, including mice, for POLR3-related leukodystrophy provide key information about disease mechanisms and are used to accelerate the development of therapeutic strategies.
We look to better understand the natural disease course of leukodystrophies and the impact on patients and their families lives through questionnaires, clinical visits, and active patient communication and discussion.
Our team is engaged as a study site in industry-sponsored clinical trials aiming at treating rare inherited neurological disorders using the latest technologies such gene therapies and antisense oligonucleotides.