Record 2023 Awards Will Advance Cures

I’m very excited to share RSRT’s press release announcing our 2023 research awards with our entire community of Rett families and donors. It was a record year, with $10.3 million awarded to new projects in pursuit of a cure for Rett. That’s the most that RSRT has ever awarded in a single year; in fact, it’s the most that any Rett organization has ever awarded in a single year. To the families that fundraise for us and to our donors—thank you! You made this possible.

What matters most, of course is how impactful those dollars will be. And that’s why I’m especially excited to tell you that I firmly believe that multiple projects we’re funding will advance to clinical trials and become new genetic therapies. So let me give you the backstory on how and why we committed $10.3 million of the precious funds donated and raised by our Rett community.

As you know, RSRT is working to cure Rett syndrome. To achieve that means addressing the underlying genetic cause of Rett – mutations in MECP2. There are a variety of strategies to accomplish that, each with their own advantages and disadvantages. RSRT’s philosophy is to drive forward in parallel as many strategies as possible to reach all MECP2 mutations. The richer our pipeline of potentially curative strategies, the greater the likelihood of success. I am confident that in time there will be multiple cures for Rett, not just one.

The best-known genetic-based strategy is traditional gene therapy where healthy genes are injected into the body to compensate for dysfunctional ones. RSRT invested millions of dollars in this approach and both the Taysha and Neurogene Rett programs got their start in RSRT’s Gene Therapy Consortium. We are cautiously optimistic that this approach will provide dramatic symptomatic relief.

Rather than adding extra copies of the MECP2 gene, other approaches correct the mutations in either the DNA, the blueprint for MECP2, or the RNA, the copy that is used to build the MECP2 protein. RNA editing and DNA base editing correct specific mutations while prime editing, an advanced form of DNA editing, can correct different mutations that are close to each other with a single therapy. As prime editing technology improves over time it will eventually be able to correct all mutations in MECP2.

In 2023 RSRT awarded substantial additional funding to the labs of Pete Beal, Adrian Bird, Guoping Feng, Erik Sontheimer, Jonathan Watts, and Scot Wolfe to advance RNA, base, and prime editing. Many elements went into the decision to fund these particular labs. First and foremost, these RSRT-funded scientists have a track record of generating high-quality, cutting-edge science and have already generated robust data worthy of being advanced. Importantly, the labs enthusiastically agreed to work in a collaborative environment rather than a siloed one. Building on the successes of the RSRT-created MECP2 Consortium and Gene Therapy Consortium this core group of scientists will exchange data and brainstorm together in the newly created RSRT Editing Consortium. In fact, advances from this key collaboration effort are already underway having kicked off with an in-person meeting earlier this month. Lastly, providing significant funding within a structured and collaborative environment with aggressive timelines to develop new genetic therapies places Rett in pole position in these world-renowned labs.

Nonprofits often provide funding, congratulate and wish the lab luck and follow up when the progress report becomes due a year later. This approach does not maximize our donor investment or ensure progress at the fastest rate possible, so this hands-off approach does not fly at RSRT. My internal research team comprised of Bob Deans, PhD, Chief Technology Officer; Jana von Hehn, PhD, Chief Scientific Officer; Randy Carpenter, MD, Chief Medical Officer, collectively has many decades of deep biopharmaceutical industry experience. Backed by the strategic foresight I’ve gained over two decades, we make a strong team uniquely capable of guiding our funded investigators toward the most efficient path to develop cures for Rett. The scientific prowess of the members of the Editing Consortium combined with RSRT’s strategic and development expertise will rapidly translate new scientific breakthroughs into therapeutics for individuals with Rett syndrome. We are very excited about this concerted effort and look forward to updating you as we progress.

In addition to the above projects, RSRT also provided funding to a Dutch biotechnology company, ProQR, for RNA editing initially focused on the R270X mutation in MECP2 with the goal to add more mutations as the technology advances. This project is in collaboration with Pete Beal.

Recognizing the importance of biomarkers for Rett, we doubled down on funding to the lab of Victor Faundez. We also provided continued funding for the Rett Syndrome Global Registry and our biorepository of patient cells.

You’ll be hearing a lot more about these projects and the scientists behind them in the weeks and months to come. I thank each and every Rett family who donates and fundraises for RSRT as well as every donor and supporter. These awards are your funds hard at work for our children.

Thank you!

List of 2023 awards:

Gene Therapy and Editing Approaches

Adrian Bird and Jacky Guy, University of Edinburgh
Correcting Rett syndrome-causing C-terminal Deletions using Adenine Base Editors
$315,502

Erik Sontheimer, Jonathan Watts, Scot Wolfe, UMASS Medical School
Base and Prime Editing Approaches for Rett syndrome
$2,343,091

Guoping Feng, MIT
Single AAV Deliverable and Transiently Inducible Base Editors for Rett syndrome
$3,734,738

Peter Beal, UC Davis
Directed RNA editing for the repair of MECP2 mutations causing Rett syndrome
$390,506

ProQR
Correction of R270X mutations in MECP2 RNA using Axiomer® Technology
$1,120,000

Michael Elowitz and Viviana Gradinaru, CalTech
Quantitative, dosage-compensated gene therapy for Rett syndrome
$500,000

Biomarkers

Victor Faundez, Emory University
Correlating Rett Syndrome Brain CSF Proteomes with Blood Plasma Profiles
$1,150,965

Victor Faundez, Emory University and Stuart Cobb, Edinburgh University
Systems Biology of Rett Syndrome Gene Therapy Outcomes (Supplement)
$103,120

Biorepository

Coriell Institute
Hosting RSRT’s Induced Pluripotent Stem Cell Collection
$105,826

Harvard Stem Cell Institute
Creating RSRT’s Induced Pluripotent Stem Cell Collection
$101,887

Sampled
Hosting RSRT’s Primary Fibroblast Collection|
$23,236

Real World Data, Biosensors, & Digital Technologies

Across Healthcare
Rett Syndrome Global Registry (Parent-reported SHARE Study)
$100,000

Emerald Innovations
Digital Technologies for the Assessment of Rett Symptoms
$20,075

Vivalink
Digital Technologies for the Assessment of Rett Symptoms
$7,446

Clinical Research Activities

Boston Children’s Hospital Rett Syndrome Research Team
Rett Clinic Support
$69,088

Montefiore Rett Syndrome Research Team
Rett Clinic Support
$50,000

Orrin Devinsky, NYU Langone
Improving Diagnostic Accuracy of Seizure and Non-Seizure Events to Enhance Clinical Care and Trial Outcomes
$50,000

Miscellaneous Funding

Adrian Bird and Stuart Cobb
University of Edinburgh
Data Analysis Equipment
$87,850