We’ve awarded $8.6 million in 2019 to preeminent researchers in our pursuit of a cure.

TRUMBULL, CT — The Rett Syndrome Research Trust (RSRT) committed $8.6 million in 2019 for breakthrough research focused on curing Rett, bringing the total research dollars invested since RSRT’s inception to $66 million.

RSRT’s mission is to accelerate the development of a cure for Rett Syndrome and MECP2 disorders. Roadmap to a Cure, launched in 2017 is a strategic research plan comprised of four pillars: Cure, Treat, Enable, and Learn. These pillars guide RSRT funding, with projects aimed at Cure, front and center, in the 2019 awards.

Rett Syndrome is a devastating neurological disorder characterized by loss of language, hand skills, and motor function. As the disorder progresses it brings breathing difficulties, seizures, anxiety, tremors, gastrointestinal and muscular skeletal problems. Rett Syndrome results from a dominant mutation in a gene on the X chromosome, MECP2, which is expressed in all tissues, but is especially abundant in the brain.

Highlights of our 2019 funding include:

• An award of $765,607 to James Wilson, MD, PhD, who heads the world’s largest academic gene therapy program at UPENN. Dr. Wilson led the discovery of the adeno-associated virus vector, AAV9, that is the current gold standard for gene therapy delivery to the brain. This latest award builds on the ongoing RSRT-funded Rett gene therapy program at UPENN with the goal of advancing a Rett gene therapy into a clinical trial in 2022.

• $3.3 million of continued funding to the MECP2 Consortium comprised of top international researchers:
  Gail Mandel, PhD, Oregon Health Sciences University; Adrian Bird, PhD, University of Edinburgh; and Michael Greenberg, PhD, Harvard University. The Consortium has made landmark discoveries creating a platform of knowledge critical in the search for a cure. The Bird lab upended the prior incomplete view of MeCP2 as a gene- specific transcriptional repressor showing that instead the protein binds broadly across the neural genome. The lab also identified a novel binding partner of MeCP2, NCOR/SMRT, opening the door to new therapeutic avenues. The Greenberg lab discovered that MeCP2 plays an important role in regulating long genes that are primarily expressed in the brain and are critical for normal brain function. The Mandel and Bird labs were the first to show that Rett symptoms could be reversed using gene therapy in symptomatic mice. The Mandel lab introduced the RNA editing field to Rett and is making remarkable progress. The MECP2 Consortium, funded by RSRT since 2011 is a highly collaborative team of scientists with a record of delivering high quality, foundational research.

• An award of $359,856 to Thorsten Stafforst, PhD, University of Tübingen, Germany, a pioneer in the field of RNA editing. Dr. Stafforst has developed a simple, efficient and specific RNA editing platform called RESTORE that doesn’t require viral delivery. Potential advantages of non-viral delivery include decreased immunogenicity and improved delivery to the brain. He will assess efficacy of the RESTORE platform to correct the mutations that cause Rett syndrome.

• An award of $275,000 to Peter Glazer, PhD, and Mark Saltzman, PhD, at Yale University for a novel non-viral delivery system. The system uses synthetic nanoparticles that are uniquely designed to target, bind and edit specific mutations.

• The Jackson Laboratory was awarded $417,690 to expand the number of mutant mouse models available for research and provide baseline characterization of these models. This award provides the foundation for what will become the “go to” facility for academia and industry alike to test potential therapeutic agents rigorously in a systematic standardized and objective fashion at a world-renowned institute.

• $520,000 awarded to Beth McCormick at the University of Massachusetts Medical School (UMass) to define gut microbiome alterations in individuals with Rett Syndrome and assess efficacy of dietary interventions to improve gut health and overall wellbeing. The study is expected to begin in the spring and will enroll girls 6 years of age and older with a documented MECP2 mutation.

“Our 2019 awards reflect RSRT’s commitment to funding the boldest research that attacks Rett Syndrome at its core,” said executive director Monica Coenraads. “I made a promise to my daughter that I won’t rest until this research can profoundly change her life. That promise extends to every child and adult with Rett or a related MECP2 disorder. I am inexpressibly grateful that we have a tremendous team helping us achieve that goal. It’s a team that includes our funded researchers, RSRT’s internal scientists, staff and trustees, the remarkably strong and tenacious families that fundraise for us, and our loyal and generous donors.”

Awards also included two projects totaling $1 million financed by the MECP2 Duplication Syndrome Fund at RSRT. Anastasia Khvorova, PhD, UMass Medical School RNA Therapeutics Institute, will be developing a therapeutic approach to reduce levels of the MECP2 protein via small interfering RNA. Ronald Cohn, MD, The Hospital for Sick Children, in Toronto will be pursuing a genome editing approach that removes the duplicated gene.

List of 2019 Awards by Strategic Roadmap to a Cure Pillar

Cure

Treat

Enable

Learn

List of 2019 Awards | MECP2 Duplication Syndrome