We know this from the reversal experiments of 2007 which proved that a cure for Rett was hypothetically possible. But it wasn't until 2013, that researchers found a tangible way to translate those original reversal experiments into something that could potentially work in a human with Rett Syndrome; gene therapy.
At that point, our partners at RSRT immediately launched the Gene Therapy Consortium, a group of four elite labs, bringing together their unique area of expertise in order to troubleshoot all the problems inherent with translating this complex lab work, into a potentially life-changing therapy for people living with Rett Syndrome.
At Reverse Rett, we financially we’ve supported RSRT’s MECP2 Consortium since our launch in 2010. We have financially supported RSRT’s Gene Therapy Consortium since its launch in 2013, with particular emphasis on the lab of Stuart Cobb in Glasgow.
All this has led to the development of RSRT’s three year plan to cure Rett Syndrome; the Roadmap to a Cure which was launched earlier this year. At the core of RSRT's plan are four cutting-edge priority approaches that are designed to cure Rett Syndrome by attacking the root cause of the disorder: MECP2.
The lead program of the Roadmap to a Cure is Gene Therapy, but all these approaches will be pursued in parallel. All are applicable to any and all MECP2 mutations and deletions.
Gene therapy is the most advanced of the four curative approaches and is the lead program.
The concept behind gene therapy is simple: delivery healthy copies of the MECP2 gene to compensate for the mutated ones. Over the past three years the results of RSRT's Gene Therapy Consortium have exceeded expectations.
The magnitude of improvement in the mouse models of Rett is much greater than that of any drug in development and suggests that significant benefit may be achieved in people. The Roadmap goals are to begin the first ever gene therapy clinical trial in people and to support development of improved second-generation gene therapy programs.
MECP2 Reactivation Girls and women with Rett have a mutation in only one of their two copies of the MECP2 gene. Like all females, one of the two MECP2 copies is randomly inactivated. The mutated gene is active and making defective protein in approximately half of all cells in the body, while the healthy copy of the MECP2 gene in those cells is silenced.
Reactivate the silent copy and theoretically Rett is cured. There is a healthy copy of MECP2 in every cell, we don’t have to deliver it, it’s already there, we just have to find a way to wake it up.
RNA Editing The possibility of editing RNA has profound therapeutic potential, but has remained largely theoretical. Focused investments by RSRT have already demonstrated the potential for correcting MECP2 mutations at the level of RNA. We are currently increasing our investment to aggressively pursue this therapeutic approach. Goals during the next three years are to improve specificity and efficiency of editing RNA in the brain and to identify optimal delivery methods.
Protein replacement RSRT is collaborating with a biotech company that has developed a technology to deliver proteins to the brain. Alternative technologies are also being developed. Covering every base RSRT's four curative approaches intervene at all three stages of the “gene to protein” process. This multi-pronged strategy greatly increases the chance of success.