During her postdoctoral studies, Dr. Geneviève Bernard first discovered the gene responsible for 4H leukodystrophy (also known as 4H syndrome), a rare disease affecting the central nervous system. Now, Dr. Bernard is once again advancing scientific studies and understanding within this realm. Reporting from Susan Schwartz of the Montreal Gazette explains that Dr. Bernard and her team recently developed the first representative mouse model of 4H leukodystrophy. 

Animal models are often used in biomedical research to evaluate physiology or responses to pathogens, environmental changes, or changes within the body. These models can play a crucial role in identifying and testing potential treatment options for a wide variety of diseases. In this case, Dr. Bernard notes that the mouse model could be used to test therapies for leukodystrophy. There is no known cure, or targeted treatment, for 4H leukodystrophy. Instead, treatment is supportive, focused on symptom management and quality-of-life. By developing the mouse model, Dr. Bernard’s team has set the stage to begin working towards therapeutic interventions for families. Learn more about animal models and how/why they are used for research here.

The mouse model for 4H leukodystrophy is described within Brain. This model shares the significant features associated with this condition to mirror what patients are experiencing. In the future, Dr. Bernard and her team are working to develop a possible gene therapy solution. If that solution is developed, it will first be evaluated on the model to determine safety and viability.

What We Know About 4H Leukodystrophy

Also known as: 4H syndrome; POLR3-Related Leukodystrophy

4H leukodystrophy is a subtype of leukodystrophy, a group of progressive diseases affecting the development of, or destruction of, the myelin sheath (the protective covering of nerve cells in the brain). The name (4H) stands for Hypodontia (missing teeth), Hypomyelination (lack of myelin), and Hypogonadotropic Hypogonadism (delayed/absent puberty). 4H leukodystrophy has been linked to mutations in four genes: POL3RA, POL3RB, POLR1C, and POL3R3K. The mutations are inherited in an autosomal recessive pattern; affected individuals inherit one defective gene from each parent.

In many cases, symptoms manifest in early childhood and may include:

• Dental abnormalities (missing teeth, teeth present at birth)
• Speech that is difficult to understand
• Absent or delayed puberty
• Short stature / overall small size
• Ataxia (impaired coordination)
• An abnormal gait with frequent tripping and/or falling
• Muscle stiffness
• Dystonia (uncontrolled muscle contractions)
• Milestone delays
• Learning disabilities
• Vision abnormalities, such as nearsightedness
• Tremors
• Seizures