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 in March 2017 we launched a bold plan to get us there. The therapeutic strategies are identified, world-class scientists recruited, and our internal team is in place to monitor and evaluate progress.
RSRT is the only organization in the world that has a comprehensive, strategic and aggressive plan for a cure in place. Do you want a cure as badly as we do? If so, then we ask for your help.
We have $2.6 Million left to raise for Roadmap to a Cure. Now's the time to be part of changing your child’s or loved one’s life. Don’t wait! Take action TODAY. Here’s what you can do...
To cure Rett we have to attack the root cause of the disorder: MECP2 mutations. We have four priority approaches that do just that. Each employs state of the art technologies undertaken by elite scientists with proven track records. To ensure a cure is achieved as quickly as possible it is imperative that each approach be pursued in parallel.
“Without RSRT championing gene therapy, we would not be where we are today.”
Brian Kaspar, PhD Chief Scientific Officer, AveXis
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.
Rather than target DNA, this approach targets the intermediate step between DNA and the protein product: RNA. This area of science is hot and exciting and RSRT is right in the middle of the action.
Leaving no stone unturned we have invested $5.7 million in two main areas: RNA editing and RNA transsplicing.
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.
Although focused on CURE we 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 monitor all treatment development programs and selectively invest in those most likely to significantly improve symptoms.
“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
RSRT plays 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 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.
We aim to facilitate the most promising clinical trials.
Clinical Trial Consortium
The Rett Syndrome Clinical Trial Consortium was launched by RSRT in the fall of 2017 with the primary objective of providing expert Rett physicians with the personnel and resources necessary to execute high-quality clinical trials in a timely and efficient manner.
We are excited to launch our first FDA-regulated trial within the Consortium in 2019 and expand our clinical research to include commercial and clinical-stage industry partners.
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 are building a bio-repository of these cells that can be freely accessed by academic and industry scientists.
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.
The $66 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
Ketamine Clinical Trial Jeffrey Neul, MD, PhD
Rett Syndrome Microbiome Study for the Advancement… Beth McCormick
Passive Monitoring of Rett Patients with the… Emerald Pilot and MC10 nPoint Development Study
Rett Syndrome Biorepository Coriell Institute for Medical Research
The generation and phenotypic assessment of mouse… Jackson Labs
RNA editing for MECP2 mutations via RESTORE Thorsten Stafforst, PhD
Correction of MECP2 Mutations with Engineered… Joseph Jacobson, PhD
Development of a cDNA/mRNA Delivery System…
Human In Vitro Models For X Chromosome… Joost Gribnau, PhD
Development of siRNA-based compounds to potently… Anastasia Khvorova, PhD
Interrogation of Genome Editing Strategies as a… Ronald Cohn, MD | The Hospital for Sick Children
Gene Therapy Consortium 1.0 Gail Mandel, PhD | Stuart Cobb, PhD | Steven Grey, PhD
Gene Therapy Consortium 2.0 Adrian Bird, PhD | Stuart Cobb, PhD | James Wilson, MD, PhD
Outcome Measures and Biomarkers Development Timothy Benke, MD, PhD | Alan Percy, MD | Daniel Tarquinio, DO, MS
A Drug-Screening Platform for the MECP2… Alysson Renato Muotri, PhD | University of California San Diego
MECP2 Consortium Adrian Bird, PhD, University of Edinburgh | Michael Greenberg, PhD, Harvard…
Gene Therapy Consortium Stuart Cobb, University of Glasgow | Steven Gray, UNC | Brian Kaspar,…
MECP2 Consortium Adrian Bird, PhD | Michael Greenberg, PhD | Gail Mandel, PhD
Clinical Trial Consortium David Lieberman & Mustafa Sahin | Eric Marsh | Jeff Neul | Alan Percy |…
Triheptanoin (UX007) | Treatment of Mitochondrial… Daniel Tarquinio, DO, MS | Center for Rare Neurological Diseases
Protein Replacement for Rett Syndrome Armagen
Gene Therapy Approach to Treating MECP2… Kevin Foust, PhD | Ohio State University
Optimizing Gene Therapy for Rett Syndrome Kathrin Meyer, PhD
A System For Dosage-independent Control of Mecp2… Michael Elowitz, PhD | Caltech
Developing a pre-clinical DNA base editing program… BEAM Therapeutics
Exploration of the Impact of Cyclodextrin on… Stephen Turley, PhD & Adam Lopez, PhD | University of Texas Southwestern…
Investigating the Potential of Antisense… Huda Zoghbi, MD | Baylor College of Medicine
Identification of Gene Modifiers that Ameliorate… Monica Justice, PhD | Hospital for Sick Children (Toronto)
Identifying Therapeutics for Treating Rett… Michael Greenberg | Harvard University
Development of an In-Vitro Cell System For… Q-State BioSciences
Modeling MECP2 Dosage in Human Cerebral Organoids Alysson Renato Muotri, PhD | University of California San Diego
RNA and Genome editing for treatment of Rett… Jonathan Watts, PhD / Erik Sontheimer, PhD / Scot Wolfe, PhD / Anastasia…
Discovery of Compounds Promoting MECP2… Andrew Napper, PhD | Nemours/A.I. duPont Hospital for Children
Reversal of Rett Phenotype: A screen for compounds… Rudolf Jaenisch, MD | Whitehead Institute
A Forward Genetic Screen to Identify Druggable… Huda Zoghbi, MD | Baylor College of Medicine
Identification of Genetic Modifiers in Rett… Jeffrey Neul, MD, PhD | University of California San Diego
RNA-editing as a gene therapy approach for Rett… Guoping Feng, PhD /Feng Zhang, PhD /Robert Desimone, PhD MIT/Broad/Harvard
New Editing Enzymes for RNA Gail Mandel, PhD | John Sinnamon, PhD
From Sensory-Perceptual Representations to… John Foxe, PhD., University of Rochester, Albert Einstein College of…
Treatment of Rett Syndrome with Lovastatin Aleksandra Djukic, MD, PhD Albert Einstein College of Medicine,…
Is MECP2 Duplication/Triplication Syndrome… Huda Zoghbi, MD | Baylor College of Medicine
Screening for drugs that can rebalance long gene… Mark Zylka, PhD | University of North Carolina at Chapel Hill
New Molecular Tools for Directed Editing of MeCP2… Peter Beal, PhD | UC Davis
Outlining the Autonomic Signature of Rett Syndrome Debra Weese-Mayer, MD & Michael Carroll, PhD | Ann & Robert H. Lurie…
Therapeutic Approaches to Reversing Forebrain and… David Katz, PhD | Case Western Reserve University
Treatment of Rett Syndrome with Copaxone Aleksandra Djukic, MD, PhD Albert Einstein College of Medicine,…
PNA Nanoparticles for Gene Editing of Rett… Peter Glazer, MD, PhD & Mark Saltzman, PhD | Yale University
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
RNA trans-splicing therapy in Rett Syndrome Stuart Cobb, PhD and Chris Sibley, PhD | University of Edinburgh
High-Content Phenotypic Screening of Existing… Christopher Gibson, PhD & Dean Li, MD, PhD | Recursion Pharmaceuticals
Readthrough of premature termination codons for… Allan Jacobson, PhD / Jonathan Watts, PhD | UMASS
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
Reactivating MECP2 Ben Philpot, PhD, Bryan Roth, PhD, UNC | Antonio Bedalov, MD, PhD, Fred…
Reactivating MECP2 Consortium Ben Philpot, PhD & Bryan Roth, PhD | Antonio Bedalov, MD, PhD | Jeannie…
Reactivation of MECP2 and CDKL5 genes by… Andrea Cerase, PhD | Queen Mary University of London
Testing Whether LM22A-4 Improves Hippocampal… Lucas Pozzo-Miller, PhD | University of Alabama Birmingham
Reactivation of MECP2 by Artificial Transcription… Raf Schmid, PhD, MSCR | University of Pennsylvania
Preclinical Studies of LM22A-4 in Mouse Models of… David Katz, PhD | Case Western Reserve University
Reactivation of MECP2 with Epigenome Editing Tools… Rudolf Jaenisch, MD | Whitehead Institute
Evaluating Cell-permeant Miniature Proteins… Alanna Schepartz, PhD | Yale University
Outcome Measures and Biomarkers Development Timothy Benke, MD, PhD | Aleksandra Djukic, MD, PhD | Alan Percy, MD |…