TheRoadmap to a Cure
Three-Year Strategic Research Plan
If you love a child with Rett Syndrome, you want the answer to one all-consuming question: Will there be a cure? We are confident the answer is YES, and we have a solid plan to get us there. But we can’t do it alone. We will need the commitment and the support of Rett families in the US and around the world. We invite you to learn about our $33 million, three-year strategic research plan.
RSRT will not be satisfied with
subtle symptom improvement.
We want a cure.
Funding needs $13,000,000
At the core of the plan are four cutting-edge priority approaches that are designed to cure Rett Syndrome by attacking the root cause of the disorder: MECP2. These approaches, which will be pursued in parallel, are applicable to any and all MECP2 mutations and deletions.
A single gene therapy treatment should be a one-time fix
Girls and women with Rett have a mutation in only one of their two copies of the MECP2 gene. Like all females, one of the two MECP2 copies is randomly inactivated. The mutated gene is active and making defective protein in approximately half of all cells in the body, while the healthy copy of the MECP2 gene in those cells is silenced. Reactivate the silent copy and theoretically Rett is cured.
There is a healthy copy of MECP2 in every cell, we don’t have to deliver it, it’s already there, we just have to find a way to wake it up.
The possibility of editing RNA has profound therapeutic potential, but has remained largely theoretical. Focused investments by RSRT have already demonstrated the potential for correcting MECP2 mutations at the level of RNA. We are currently increasing our investment to aggressively pursue this therapeutic approach.
Goals during the next three years are to improve specificity and efficiency of editing RNA in the brain and to identify optimal delivery methods
We are collaborating with a biotech company that has developed a technology to deliver proteins to the brain. Alternative technologies are also being developed. We will monitor, evaluate and pursue worthy approaches.
Covering Every Base
Our four curative approaches intervene at all three stages of the “gene to protein” process. This multi-pronged strategy greatly increases our chances of success.See all cure projects
Funding needs $3,300,000
Although focused on CURE we will also monitor treatments that have the potential to improve quality of life.These approaches do not directly target the root cause of Rett, MECP2, and therefore cannot be considered cures. All current and past clinical trials for Rett fall into this category. We will monitor all treatment development programs and selectively invest in those most likely to significantly improve symptoms.See all treat projects
“By attracting the best scientists and clinicians, RSRT is in pole position to deliver on the pre-clinical work showing that Rett Syndrome will be a curable disorder.”
Adrian Bird, PhD RSRT TRUSTEE & SCIENTIFIC ADVISOR Buchanan Professor of Genetics, University of Edinburgh
Funding needs $9,200,000
RSRT will play a vital role in creating the conditions that will enable the most impactful pharmaceutical and biotech industry investment in Rett research. Historically, approval of new drugs has been hampered by the absence of several key resources: 1) Lack of accurate, FDA-approved outcome measures for clinical trials, including devices that can accurately measure these outcomes, 2) The ability to identify the right patients for the right trials, and 3) Lack of human cells from patients to test new therapies in the lab.
The following projects will address these issues and drive industry investment in Rett research. They are designed to remove barriers of entry and lower risk, thereby shortening the timeline for drug development and facilitating the approval of novel therapeutics.
Testing Therapies in Patient Cells
Because no animal model can completely duplicate the human disease it is important to verify results from animal studies using human cells. Today, technology exists to convert skin or blood cells collected from individuals with Rett into brain cells. These cells can be used to replicate results observed in animal models. Since brain cells can be generated from any individual with Rett, this technology also allows us to assess whether there are significant differences among individuals in response to a new therapy. We will build a bio-repository of these cells that can be freely accessed by academic and industry scientists.See all enable projects
Funding needs $4,500,000
Our strategic investments in basic science have led us to this promising new stage of research in which we can realistically pursue the curative approaches just described. We live in an exciting time: scientific advances are continuously providing insights that could open doors to new and better ways to treat your children. Therefore it is critical for RSRT to continue to LEARN by closely monitoring scientific breakthroughs and novel technologies that can be put to work to defeat Rett.See all learn projects
The $41 million that we have strategically awarded to research to date has resulted in the knowledge, data, and partnerships that inform and guide this Roadmap to a Cure.
RSRT sets the research agenda by proactively identifying and monitoring promising therapeutic areas, seeking out scientific and industry partnerships and working closely with them to advance programs through the drug development pipeline.
The RSRT team is lean and fiercely focused on what matters most: healing our children as quickly as possible.
“The day my daughter was diagnosed I made her a promise that I wouldn’t rest until we found a cure. We have an opportunity now, as never before, to drive the science that will change lives.”
Monica Coenraads EXECUTIVE DIRECTOR Rett Syndrome Research Trust
The Time is Now
Whether you live in the U.S., Europe, South America or elsewhere, we need you. We cannot rely on governments or industry or anyone else to cure our children.
It’s up to us. Help us change lives and complete the form below.
“We wanted to do everything in our power to help RSRT carry out Roadmap to a Cure so we made a pledge that goes above and beyond what we would normally contribute. No investment is more important for our daughter and for all who live with Rett Syndrome. We’re proud to be Roadmap Trailblazers.”
Jim & Audra Small ROADMAP TRAILBLAZERS
MEET THE TRAILBLAZERS
Optimizing Gene Therapy for Rett Syndrome Kathrin Meyer, PhD
Reactivation of MECP2 by Artificial Transcription… Ben Philpot, PhD | University of North Carolina
Reactivation of MECP2 with Epigenome Editing Tools… Rudolf Jaenisch, MD | Whitehead Institute
Identifying Therapeutics for Treating Rett… Michael Greenberg | Harvard University
Development of an In-Vitro Cell System For… Q-State BioSciences
Reversal of Rett Phenotype: A screen for compounds… Rudolf Jaenisch, MD | Whitehead Institute
Protein Replacement for Rett Syndrome Armagen
Spliceosome-Mediated RNA Trans-Splicing Therapy… Stuart Cobb, PhD | University of Edinburgh
Modeling MECP2 Dosage in Human Cerebral Organoids Alysson Renato Muotri, PhD | University of California San Diego
A Drug-Screening Platform for the MECP2… Alysson Renato Muotri, PhD | University of California San Diego
Triheptanoin (UX007) | Treatment of Mitochondrial… Daniel Tarquinio, DO, MS | Emory University | Children's Pediatric…
Outcome Measures and Biomarkers Development Timothy Benke, MD, PhD | Aleksandra Djukic, MD, PhD | Alan Percy, MD |…
From Sensory-Perceptual Representations to… John Foxe, PhD., University of Rochester, Albert Einstein College of…
Exploration of the Impact of Cyclodextrin on… Stephen Turley, PhD & Adam Lopez, PhD | University of Texas Southwestern…
Discovery of Compounds Promoting MECP2… Andrew Napper, PhD | Nemours/A.I. duPont Hospital for Children
Treatment of Rett Syndrome with Lovastatin Aleksandra Djukic, MD, PhD Albert Einstein College of Medicine,…
Gene Therapy Approach to Treating MECP2… Kevin Foust, PhD | Ohio State University
Investigating the Potential of Antisense… Huda Zoghbi, MD | Baylor College of Medicine
A Forward Genetic Screen to Identify Druggable… Huda Zoghbi, MD | Baylor College of Medicine
Is MECP2 Duplication/Triplication Syndrome… Huda Zoghbi, MD | Baylor College of Medicine
Outlining the Autonomic Signature of Rett Syndrome Debra Weese-Mayer, MD & Michael Carroll, PhD | Ann & Robert H. Lurie…
Exploring the Link Between MeCP2 and Gut… Ali Khoshnan, PhD & Sarkis K. Mazmanian, PhD | California Institute of…
Testing NR2A and NR2B NAMs in the mouse models of… Michela Fagiolini, PhD | Boston Children’s Hospital
Therapeutic Approaches to Reversing Forebrain and… David Katz, PhD | Case Western Reserve University
Testing Whether LM22A-4 Improves Hippocampal… Lucas Pozzo-Miller, PhD | University of Alabama Birmingham
Preclinical Studies of LM22A-4 in Mouse Models of… David Katz, PhD | Case Western Reserve University
Screening for drugs that can rebalance long gene… Mark Zylka, PhD | University of North Carolina at Chapel Hill
Clinical Development of NLX-101 in Rett Syndrome;… Mark Varney, PhD | Neurolixis
Systems Genetics Approach toward Understanding… Terry Magnuson, PhD | University of North Carolina at Chapel Hill
Identification of Genetic Modifiers in Rett… Jeffrey Neul, MD, PhD | University of California San Diego
Identification of Gene Modifiers that Ameliorate… Monica Justice, PhD | Hospital for Sick Children (Toronto)
Treatment of Rett Syndrome with Copaxone Aleksandra Djukic, MD, PhD Albert Einstein College of Medicine,…
Low-dose Ketamine for the Treatment of Rett… David M. Katz, PhD, Case Western Reserve University & Dan Sessler, MD,…
Clinical Trial Consortium David Lieberman & Mustafa Sahin | Eric Marsh | Jeff Neul | Alan Percy |…
Reactivating MECP2 Consortium Ben Philpot, PhD & Bryan Roth, PhD | Antonio Bedalov, MD, PhD | Jeannie…
MECP2 Consortium Adrian Bird, PhD | Michael Greenberg, PhD | Gail Mandel, PhD
Gene Therapy Consortium Stuart Cobb, PhD | Steven Gray, PhD | Gail Mandel, PhD | Alysson Muotri,…
Outcome Measures and Biomarkers Development Timothy Benke, MD, PhD | Alan Percy, MD | Daniel Tarquinio, DO, MS