RSRT launches program to advance genetic therapies for Rett

Roadmap to Cures seeks $40M to move 3 therapies to clinical trials by 2028

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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Rett Syndrome Research Trust (RSRT) has launched an initiative to advance three genetic medicines for Rett syndrome to clinical trials by 2028.

Called Roadmap to Cures, it seeks to raise $40 million over the next four years to help select and develop the therapies and is based on the new MECP2 Editing Consortium, a collaboration among six labs working on next-generation gene- and RNA-editing therapies for Rett syndrome.

RNA molecules include messenger RNA which carries instructions from genes and works as a template to produce proteins, and other RNA regulatory molecules that regulate protein production.

“Next-generation medicines have the potential to provide even more benefit and expand the reach of a cure to more patients,” Monica Coenraads, RSRT’s CEO and a parent to a child with Rett, said in an organization press release.

Rett syndrome is mainly caused by mutations in the MECP2 gene that impair the function of MeCP2, a protein that regulates the activity of other genes. MeCP2 plays an important role in the brain, by helping maintain the connection between nerve cells, and loss of the protein in Rett impairs nerve cell growth and connectivity, leading to disease symptoms.

However, too much MeCP2 can be toxic to cells so its levels need to be finetuned. Both gene and RNA editing do not interfere with the cells’ ability to modulate MeC2 protein levels, which makes these approaches attractive, according to the press release.

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Goal is to speed development of therapies using CRISPR-based technology

RSRT’s initiative aims to accelerate the development of therapies, using editing systems such as base editing and prime editing, both based on CRISPR technology. Whereas base editing corrects single mutations in a single building block of the genetic code, prime editing can correct multiple mutations.

A team including RSRT staff, advisers, and experts in genomic medicine, clinical trial design, and regulation are working toward the goal of accelerating treatment development. The Rett community is encouraged to contribute through fundraising events and crowdfunding campaigns.

“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,” said Robert Deans, PhD, RSRT’s chief technology officer.

According to the organization’s plan, the three genetic medicines should be selected by 2025, and safety and dosing studies would be completed by 2026. Then, following clearance from the U.S. Food and Drug Administration, clinical trials can start in 2028.

RSRT launched Roadmap to Cures in 2017 to advance genetic medicine approaches targeting the root cause of Rett. The organization has invested more than $11 million in two gene therapy programs for Rett that are now in clinical trials: Neurogene’s NGN-401 and Taysha Gene Therapies’ TSHA-102. Both are designed to provide working versions of the MECP2 gene to patients’ cells.

“Given the dramatic nature of symptom reversal in Rett syndrome animal models, we are optimistic that targeting the underlying genetic cause will be transformational,” Coenraads said.

“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,” she added.