Trumbull, CT - The Rett Syndrome Research Trust (RSRT) has taken a significant stride in the pursuit of innovative genetic medicines for Rett syndrome by establishing the MECP2 Editing Consortium. Mutations in MECP2 cause Rett syndrome, a debilitating neurological disorder that causes a lifetime of severe disabilities. The consortium comprises six distinguished labs, including Adrian Bird, PhD and Jacky Guy, PhD from the University of Edinburgh, Erik Sontheimer, PhD, Jonathan Watts, PhD and Scot Wolfe, PhD from University of Massachusetts Chan Medical School, Guoping Feng, PhD and Chenjie Shen, PhD from Massachusetts Institute of Technology, and Peter Beal, PhD from the University of California, Davis. The editing consortium, supported with a $7 million investment from RSRT, is inspired by the prior success of RSRT’s Gene Therapy Consortium which laid the foundation for the current gene therapy trials. RSRT is the largest funder of Rett research with more than $77 million awarded since 2008 to advancing cures.
The consortium's inaugural meeting earlier this year set an ambitious agenda to advance editing programs to clinical trials. The meeting, led by RSRT's Chief Technology Officer, Robert Deans, PhD, was designed to foster transparency, collaboration, and cross-learnings, and delved into key objectives such as DNA and RNA editing pipelines, delivery options, company partnerships, and engagement with the FDA.
Presentations and discussions around these cutting-edge programs established ambitious goals to generate clinical candidates on fast-tracked timelines and showcased the consortium's commitment to accelerating advancements in editing technologies. Augmenting the expertise of the 6 labs, the meeting also included a presentation from David Liu's lab at Harvard on the latest advances in gene editing technologies, emphasizing the collaborative spirit that will guide the consortium’s efforts.
The decision to launch the consortium was inspired by the success of RSRT’s Gene Therapy Consortium that led to the development of two gene therapy candidates and laid the foundation for the first gene therapy clinical trials in Rett, currently ongoing in the US and Canada with planned expansions. The MECP2 Editing Consortium is similarly poised to shape the future landscape of DNA and RNA editing for Rett, fostering collaboration and driving the development of additional groundbreaking therapies toward the clinic.
Enhancing the editing expertise of the consortium labs is the collective translational medicine experience of RSRT’s research team. Robert Deans, CTO, Randy Carpenter, MD, Chief Medical Officer and Jana von Hehn, PhD, Chief Scientific Officer, bring decades of industry experience, FDA interactions, clinical trial operations and program management support.
“The MECP2 Editing Consortium's formation is propelled by the momentum of genetic medicines and marks another significant leap forward in the pursuit of cures for Rett syndrome,” said Robert Deans. “By pooling the collective expertise of these world-class labs, we are expanding shots on goal for cures and expediting the development of editing technologies for Rett. I’m very much looking forward to working with everyone in the consortium as the programs advance toward the clinic.”
About the Labs
Adrian Bird and Jacky Guy from the University of Edinburgh are pivotal figures in the field of Rett syndrome. Bird discovered MECP2, the gene responsible for Rett syndrome when mutated, in the early 1990s and has since contributed greatly to the understanding of its function. In 2007 Bird and Guy published the groundbreaking reversal experiment. In the consortium, Bird and Guy are focusing on developing a single base editing therapeutic for C-terminal mutations which encompass 10% of Rett cases.
Erik Sontheimer, Jonathan Watts, and Scot Wolfe from UMass Chan Medical School are prominent researchers recognized for their significant contributions to the field of molecular biology and gene editing. Sontheimer is renowned for his pioneering work on CRISPR-Cas systems, while Wolfe's expertise lies in gene editing therapeutics. Watts’ expertise is in the field of oligonucleotide therapeutics and RNA chemistry. Together, they form a formidable team. In the consortium they will advance base editing for specific mutations and explore the potential of prime editing, a cutting-edge technology, for editing multiple mutations with a single therapeutic.
Guoping Feng at MIT is a distinguished researcher with impactful contributions to neuroscience and molecular biology. Feng has made significant strides in the study of synaptic function, neural circuits, and neurodevelopmental disorders. Chenjie Shen, lead scientist on the project, has excelled in the field of neurobiology, focusing on neural circuitry and molecular mechanisms related to behavior. In the consortium, Feng and Shen will focus on developing smaller, self-inactivating base editors, innovating new viral vectors, and conducting comprehensive tests on editases in both cellular and animal models in a multi-pronged approach to correct MECP2 mutations.
Peter Beal from UC Davis is recognized for significant contributions in the field of RNA biochemistry and chemical biology. His work often focuses on RNA modification enzymes, RNA editing and structure. Beal has conducted extensive research on adenosine deaminases that act on RNA (ADARs), enzymes responsible for RNA editing by converting adenosine to inosine. His expertise encompasses the study of RNA modifications and their impact on cellular processes, shedding light on fundamental aspects of RNA biology. In the consortium, Beal will advance ADAR editing to target specific MECP2 mutations.
About Rett Syndrome Research Trust
RSRT is the patient advocacy organization working to cure Rett syndrome. As the largest funder of Rett syndrome research worldwide, RSRT has played a vital role in initiating and evolving the trajectory of progress toward a cure. All genetic therapies in development by biopharmaceutical companies have leveraged discoveries and resources made possible by RSRT. Learn more at reverserett.org.
About Rett Syndrome
Rett syndrome is a genetic childhood neurological disorder caused by random mutations of the MECP2 gene on the X chromosome. The disorder affects predominantly girls but can rarely also affect boys. Symptoms typically become apparent between the ages of 12 to 18 months. Rett syndrome is devastating as it deprives toddlers of speech, hand use, and normal movement often including the ability to walk. As childhood progresses the disorder brings anxiety, seizures, tremors, breathing difficulties, and severe gastrointestinal issues. While their bodies suffer, it is believed that their cognitive abilities remain largely intact. Although most children survive to adulthood, they require total round- the-clock care.