New Rett syndrome research development shows great promise for gene therapy.
New Mouse = New Hope in Xi Research
Rettsyndrome.org is pleased to provide a recent update on HeArt Award recipient and investigator Jeannie T. Lee, MD PhD of Massachusetts General Hospital. Dr. Lee’s team has developed a new female mouse model that shows great promise in inactive X-chromosome research for Rett syndrome.
The results, published in the Proceedings of the National Academy of Sciences, prove the newly developed female mouse model produces more Rett-like symptoms (i.e., repetitive behaviors, motor weakness, tremors, and gait disturbance) — an improvement over previous mice with a mixed expression pattern for the Mecp2 mutation. Dr. Lee’s team observed that expression of 5-10% normal MeCP2 protein in the brain resulted in improved motor skill and extended lifespan 5-8 fold. Thus, the study indicates possible therapeutic benefit even when MeCP2 protein levels do not reach 100% in every brain cell.
Impact on Future Research
Rett syndrome is caused by mutations in the MECP2 gene located on the X chromosome. Females carry two X chromosomes, but in Rett syndrome, one X chromosome is inactivated randomly – through a process called X-inactivation – silencing the whole chromosome. It is thought that in Rett syndrome, the normal copy can be unsilenced by reactivation of the X chromosome.
Dr. Lee’s mouse (Tsix-Mecp2) may be more sensitive to compounds that have a positive effect on Rett-like symptoms in mice and may be used in future preclinical trials for compounds that reactivate the silenced, normal copy of Mecp2.
This initial development allows specific aims from the Rettsyndrome.org HeArt award to be studied more effectively.
Dr. Lee, the senior author of the study, added, “We are very grateful to Rettsyndrome.org for providing critical funding to spearhead this work. A most exciting finding to arise from the mouse model which has not been so easy to recapitulate in other systems is the repetitive and self-injurious behaviors that typify Rett syndrome. Our female mouse model now sets the stage for us to test candidate drugs for the X-reactivation approach that we have been building towards for the past several years.”
“Dr. Lee’s research builds a foundation for additional research, but more importantly, gives hope,” says Dr. Kaminsky.“This new report provides additional evidence that restoring MECP2 will alleviate symptoms of Rett syndrome which we hope will translate to an improved quality of life to those individuals affected by this disorder.”
Rettsyndrome.org is very proud of Dr. Lee’s work.
Rettsyndrome.org Funded Investigator and HeART award recipient Jeannie T. Lee, MD PhD Institution: Massachusetts General Hospital
Related area of study: Reactivation of the inactive normal MECP2 gene