Reversal of Neurological Defects in a Mouse Model of Rett Syndrome

TLDR

Rett syndrome, an autism spectrum disorder caused by mosaic mutant MECP2 expression in neurons, is not neurodegenerative because neurons do not die. The study investigates whether phenotypic reversibility is achievable by repairing viable but defective neurons in Rett syndrome. In a mouse model, activating MeCP2 expression robustly reverses advanced neurological symptoms in both immature and mature adults.

Abstract

Rett syndrome is an autism spectrum disorder caused by mosaic expression of mutant copies of the X-linked MECP2 gene in neurons. However, neurons do not die, which suggests that this is not a neurodegenerative disorder. An important question for future therapeutic approaches to this and related disorders concerns phenotypic reversibility. Can viable but defective neurons be repaired, or is the damage done during development without normal MeCP2 irrevocable? Using a mouse model, we demonstrate robust phenotypic reversal, as activation of MeCP2 expression leads to striking loss of advanced neurological symptoms in both immature and mature adult animals.