RSRT Launches "Roadmap to Cures" to Advance Next-Generation Genetic Medicines into Clinical Trials

Trumbull, CT Rett Syndrome Research Trust (RSRT), the organization working to cure Rett syndrome, announced the launch of a bold new initiative: Roadmap to Cures.The initiative seeks to raise $40 million over the next four years to fund breakthrough innovation for Rett syndrome through the selection and development of three genetic medicines that attack the root-cause of this rare disease, and advance them into clinical trials by 2028. Roadmap to Cures brings together the latest genome-editing technology with RSRT’s in-house expertise.

“Given the dramatic nature of symptom reversal in Rett syndrome animal models, we are optimistic that targeting the underlying genetic cause will be transformational. RSRT’s original Roadmap to a Cure and Gene Therapy Consortium laid the foundation for the current gene therapy trials underway for Rett syndrome,” says Monica Coenraads, RSRT Chief Executive Officer and Rett parent. “While we’re extremely excited about these clinical trials, developing cures for Rett syndrome is an iterative process. Next-generation medicines have the potential to provide even more benefit and expand the reach of a cure to more patients. Time is of the essence and the greatest likelihood of achieving cures in Rett is to advance, in parallel, as many shots on goal as possible. That is the goal of Roadmap to Cures.”

Rett Syndrome and the Goldilocks Problem

Rett syndrome is a rare genetic neurodevelopmental disorder that occurs primarily in females following a near normal development in the first two years of life. Rett is caused by mutations in the MECP2 gene (Methyl-CpG Binding Protein 2). Too little functioning MECP2 leads to Rett syndrome. But too much MECP2, as in MECP2 duplication syndrome, also leads to significant neurological problems. This is the Goldilocks problem — the level of MECP2 needs to be just right.

Cells have multiple mechanisms for fine-tuning how much of a given protein is made. When the cell’s own genetic code is corrected, via DNA or RNA editing, the cell’s natural mechanisms to fine-tune the amount of MECP2 protein remain intact, making these genetic approaches attractive.

Next-Generation Editing

RSRT’s new MECP2 Editing Consortium is a critical component of Roadmap to Cures. The Consortium is a collaboration among six labs, aimed at creating DNA and RNA editing therapies for Rett syndrome. The member labs’ expertise includes CRISPR-based genome-editing systems like base editing and prime editing and the ADAR RNA editing system.

Base and prime editing are versions of CRISPR where only one strand of the DNA helix is cut, minimizing the risk of unintended changes to the DNA. In RNA editing, no changes are made to the DNA. Instead, the RNA copy of the gene is edited, and if it is ineffective or if there are harmful side effects, it can be discontinued. Both DNA and RNA editing allow cells to naturally modulate the level of MECP2 protein, just like they do in individuals without Rett syndrome.

From Bench to Bedside

Bringing a potential cure from the lab bench, into the clinic through clinical trials, and ultimately to the world’s patient populations is a complex process. Once a researcher has an idea for a medicine, it typically takes many years to complete the research required to get regulatory approval to start the first clinical trial.

With Roadmap to Cures, RSRT is accelerating the timeline, with the plan to get three new next-generation therapies into clinical trials by 2028. To accomplish this, RSRT is actively collaborating on strategic plans to bring research into clinical trials. RSRT’s internal team of staff and advisors bring decades of biotech industry and clinical trial experience. RSRT also has a large network of outside experts in genomic medicine, clinical trial design, and regulation to tap as needed.

“RSRT doesn’t just write checks,” says Robert Deans, PhD, RSRT’s Chief Technology Officer. “RSRT is uniquely positioned in the Rett world with staff and advisors who have deep drug development and genetic medicine experience to effectively guide translational research and advance cures.”

Get Involved

The success of Roadmap to Cures ultimately depends on the Rett community coming together and inspiring their networks to give through fundraising events and crowdfunding campaigns. Join the RSRT community to stay up-to-date and get involved!