Physicians and families caring for individuals with Rett syndrome clearly need better therapeutic options. During my short tenure, I have been particularly encouraged by breakthrough scientific advances that may ultimately enable therapeutics directly targeting the cause of Rett syndrome – insufficient MeCP2 protein (e.g., gene therapy, X-reactivation, protein replacement). Although these programs are still in relatively early stages and success will require additional scientific advances, the pace of progress is encouraging.
Equally impressive is the surge in interest from pharmaceutical and biotechnology companies. Because I have not been able to access study reports for most of these compounds, it is impossible for me to accurately assess which, if any, of the drugs in development are most likely to demonstrate meaningful efficacy.
Regardless, experiences in other disease areas suggest that encouraging efficacy data in model animals does not reliably predict meaningful efficacy in humans. Some of the failures are clearly because the drug does not have efficacy in humans. However, the lack of sensitive outcome measures may also be to blame for some of these failures. Specifically, trial participants improved in meaningful ways, but these improvements were not captured on the efficacy measures. It’s absolutely critical that we improve the effectiveness and efficiency of future clinical trials, and that’s why a primary focus of mine during these first three months has been to launch the Outcome Measures and Biomarker Development consortium. This is a key effort if we are to improve the translation of lab discoveries into medications your children can benefit from. In doing so we reduce drug development risks and encourage investment from industry. This is a major goal at RSRT.
On a cautionary note, if all of the interested companies actually move forward, recruitment demands of competing trials may soon exceed capacity of the existing clinical research infrastructure. I, therefore, believe it timely, for all of us in the Rett community to begin considering how best to prioritize trial participation. The dilemma, therefore, is whether and how we can best anticipate this possibility and work together to best serve individuals with Rett Syndrome and their families.
It is my sincere hope that we will be able to work together to accelerate the translation of scientific discoveries to improve the lives of your loved ones. I look forward to hearing your thoughts and hope to continue this conversation in the weeks and months to come.
DNA editing has taken the science world by storm with hundreds of labs around the world working in this area. I am very excited about the possibility of correcting MECP2 mutations as this strategy should eliminate risks associated with overexpression that could come from gene therapy and/or protein replacement. DNA editing, however, has not yet advanced sufficiently to be applied to neurological diseases such as Rett Syndrome. Simply put DNA editing involves two steps 1) facilitating a break in the patient’s DNA where the mutation exists 2) fixing the break with the proper nucleotide sequences. For now step 1 is doable but the cells that can be fixed is still small, especially in cells that are not rapidly dividing like brain cells. Although neurological diseases are not yet low hanging fruits for DNA editing, numerous scientific teams are focused on overcoming these challenges and progress in this field is moving at lightening speed so stay tuned.
I would recommend that you daughter have MECP2 testing. There is additional testing that has become available since your daughter was analyzed. Does she have a neurologist that you can discuss testing with? If you need help with this please contact Monica Coenraads at firstname.lastname@example.org