Genetic Therapy Approaches in Rett syndrome - an update (Georgian)

In this talk, Stuart Cobb will provide an overview of advances in gene therapy approaches in Rett syndrome. 

Rett syndrome is a genetic disease caused by mutations in the MECP2 gene. The underlying cause of disorder is therefore a fundamental deficiency in the level of functional MeCP2 protein in the body. Animal studies predict that restoring MeCP2, especially to the nervous system, can rescue many aspects of the disorder. Since the original scientific reports of genetic rescue in mice, significant efforts have been made to develop ways by which levels of MeCP2 can be restored as a therapy for treating individuals with Rett syndrome.  

Animal studies have been instructive in identifying key cells and systems to target with genetic therapies as well as periods during development when it is possible to intervene therapeutically. Studies have also explored the levels of MeCP2 protein restoration required to produce measurable therapeutic effects in experimental models of Rett syndrome. Conventional gene replacement therapy for Rett syndrome is faced with the challenge that MECP2 is a dosage sensitive gene, with both animal data and the human duplication disorder suggesting that MeCP2 levels need to be kept within a tolerable range to avoid toxicity associated with overexpression. For this reason, activities have focused on gene therapy technologies that manage to regulate the level of MeCP2. In addition to significant progress being made in regulated gene replacement therapy, advances are being made in alternative genetic approaches including the correction / editing or readthrough of Rett-causing mutations as well as the activation of the backup MECP2 gene on the inactive X chromosome. Overall there has been an acceleration of these efforts with many programs moving from academic research laboratories into biotechnology and pharmaceutical companies. As a result, we are now seeing the first genetic therapies entering clinical trials.