New Insights into Rare Disorder May Aid Quest for Treatments

Research led by Dr Martha Koerner (School of Biological Sciences) has resulted in fresh insights into the rare genetic disorder known as MeCP2 duplication syndrome, which mainly affects boys and leads to severe intellectual disability, seizures and impaired motor function. 

Scientists have examined molecular details of the biological causes behind the disorder, which is caused by duplication of a section of DNA, including a gene known as MeCP2. The same gene is linked with Rett syndrome, a neurological disorder that affects mostly girls.  Research conducted in mice found that disease symptoms depend on a key part of the MeCP2 protein binding to another set of proteins known as NCoR in excess. However, when researchers examined a key component of NCoR that is known to interfere with DNA, they were surprised to find that removing this part had no effect on symptoms. This suggests that drugs targeting this component’s function would not relieve the condition. 

Research is now focused on drugs that could block the interaction between MeCP2 and NCoR, as a way to prevent the symptoms associated with an excess of protein.

This research is published in Genes and Development and was funded by Wellcome, the Rett Syndrome Research Trust and the Medical Research Council. 

Dr Martha Koerner said "We have effectively ruled out a key possible biological mechanism behind duplication syndrome. Our research points towards other avenues that might prove fruitful in the quest for treatments."