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.
These approaches, which will be pursued in parallel, 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.
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.
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.
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.