Adrian Bird, PhD, University of Edinburgh | Michael Greenberg, PhD, Harvard University | Gail Mandel, PhD, Oregon Health & Sciences University
As always at RSRT, our funded projects are aimed at developing effective treatments and a cure for Rett Syndrome. But one of the key roadblocks to achieving this has been a lack of knowledge about the MeCP2 protein and how it functions. In 2011 RSRT decided to conduct an experiment of our own. Take three world-class laboratories and give them the necessary financial resources and infrastructure to tackle a question that no one yet has been able to answer: what does the MeCP2 protein do?
Four years later the Consortium members are getting closer to that answer and have made the following discoveries along the way— discoveries that could prove to be invaluable to how we will ultimately change the lives of girls and women afflicted with Rett:
- It was known that MeCP2 binds to DNA in brain cells, but the Consortium showed that MeCP2 has a binding partner, called NCOR, that is known to silence genes. Importantly, the Consortium showed that mutations that disrupt the ability of MeCP2 to bind to NCOR are associated with Rett in people, thus lending support for the essential nature of this interaction.
- MeCP2 is modulated by phosphorylation for normal nervous system function.
- The Consortium has shown that gene therapy can reverse symptoms in symptomatic female Rett mice. This work is being actively followed up by a dedicated “Gene Therapy Consortium” also funded by RSRT.
- As yet unpublished work is shedding light on the crucial question of which genes in the brain are controlled by MeCP2. It may be possible to target these genes via specific drugs.