This promising strategy aims to cure Rett by activating a backup copy of MECP2 present in all female cells.
Our initial efforts at MECP2 reactivation were focused on finding small-molecule drugs that could achieve the desired effect. Scientists designed cell lines that could detect MECP2 gene reactivation, then tested hundreds of thousands of compounds using high-throughput robotic equipment. RSRT-funded scientists involved in this effort include Dr. Benjamin Philpot, PhD, Dr. Bryan Roth, MD, PhD, and Dr. Terry Magnuson, PhD, at the University of North Carolina at Chapel Hill; Dr. Jeannie Lee, PhD, at Harvard; Dr. Antonio Bedalov, MD, PhD, at the Fred Hutchinson Cancer Research Institute; Dr. Michael Green, MD, PhD, at the University of Massachusetts; Professor Joost Gribnau at Erasmus in the Netherlands; and Dr. Andrea Cerase, PhD, from the Queen Mary University of London.
Biologic Solutions to Reactivation
In recent years researchers from around the world generated additional data that made it possible to better understand how the X chromsome becomes inactivated. This additional data made it possible to begin designing biologic strategies for MECP2 reactivation. These strategies necessitate the ability to, first, target the specific spot on the X chromosome where the inactive MECP2 resides and, second, be able to bring molecules that can remove certain chemical tags from MECP2 that keep it silenced. The hope is to be able to effectively and efficiently deliver this therapeutic to the brain in a "one-and-done" manner.