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Stimulate the generation of myelin, a therapy for the CHARGE Syndrome?

CHARGE syndrome is a rare genetic disease (1/10 000 births) caused by mutation of a copy of CHD7 gene resulting in many defects. This syndrome is particularly recognized as the major cause of deafness and congenital blindness. In affected children, neurological disorders increase with age. The team of Dr. Parras to the ICM has shown that this anomaly would be linked to a deficient myelination. Their findings indicate that CHD7 gene is essential for the maturation of oligodendrocytes and myelin formation. This new potential therapeutic target could help develop new treatments for people suffering from diseases due to defects in myelination.

 

 

CHARGE syndrome is manifested by numerous birth defects: malformations of the eye, heart, nose, delayed growth and psychomotor development, genito-urinary problems, ear abnormalities. Most patients with CHARGE syndrome show alterations in the central nervous system, with defects in white matter and the formation of the myelin sheath, a substance that surrounds and protects axons allowing the rapid transmission of information in the nervous system. This demyelination that occurs in the brain but also in the spinal cord is part of the cause, depending on its location, engines, sensory disorders, balance, visual...


The myelin sheaths are produced by the brain cells called oligodendrocytes. Formed from immature precursors that are found throughout the brain, these cells must pass an immature state to a mature state. This process requires activation of genes involved in the synthesis of myelin. For this activation occurs, the chromatin must be loosened so that the DNA of these genes is accessible: is called chromatin remodeling. The CHD7 protein is a factor of chromatin remodeling, it has proven to play a major role in the maturation of oligodendrocytes.


The team of Dr. Parras studied in a mouse model, the role of CHD7 in the differentiation of oligodendrocytes and myelin formation. They showed that if CHD7 is absent, oligodendrocytes remain blocked in an immature state, which causes defects in myelination observed. CHD7 is necessary for the maturation of oligodendrocytes and is decisive for the formation and repair of myelin. The mechanisms activated by CHD7 could be therapeutic targets to allow regeneration of myelin in patients with CHARGE syndrome but also for patients with loss of myelin, as in the case of multiple sclerosis.