RSRT Invests an Additional $3.1 Million in the Plan for a Rett Syndrome Cure

The Rett Syndrome Research Trust (RSRT) is dedicating a further $3.1 million to drive forward the CURE 360 agenda aimed to cure Rett syndrome by continuing to fund the most promising research and investing in a new potentially curative strategy in 2022. RSRT’s CURE 360 plan focuses on translating laboratory discoveries about the reversibility of Rett symptoms in mice into clinical successes by incentivizing and attracting biopharmaceutical companies to work on a cure. After rigorous evaluation by RSRT’s board and scientific advisors, the most recent awards reflect the organization’s commitment to rigorous science and promising business development.

Rett syndrome is a rare, devastating neurological disorder characterized by loss of language, hand skills, and motor function that primarily affects females. As the disorder progresses it brings breathing difficulties, seizures, anxiety, tremors, and gastrointestinal and muscular skeletal problems. Most people with Rett syndrome live into adulthood, requiring round-the-clock care. Rett syndrome results from a mutation in the MECP2 gene on the X chromosome.

RSRT will continue its investment in MECP2 reactivation efforts by Antonio Bedalov, MD, PhD, and Kyle Fink, PhD, of the Fred Hutchinson Cancer Research Institute and University of California, Davis, respectively, with an award of more than $1 million. MECP2 reactivation attempts to awaken the dormant, healthy MECP2 gene on the X chromosome in enough cells to reverse Rett symptoms. This funding deepens RSRT’s investment in MECP2 reactivation, one of six genetic-based strategies for a cure, by adding Dr. Fink, who brings expertise from success reactivating a different gene on the X chromosome, to the work and knowledge that Dr. Bedalov has been generating with long-standing RSRT funding. RSRT will continue to look for ways to expand investment in MECP2 reactivation.

Victor Faundez, PhD, of Emory University, has been awarded more than $500,000 for the second phase of his research to identify a Rett syndrome biomarker in spinal fluid. Previous RSRT funding identified differences in certain molecules in the spinal fluid of healthy individuals compared to spinal fluid from people with Rett, and in Rett mouse models compared to normal mice. In this next phase of study Dr. Faundez will determine if these potential biomarkers respond to gene replacement therapy. Through an RSRT-facilitated collaboration between Dr. Faundez and Stuart Cobb, PhD, of the University of Edinburgh, this second phase will also correlate the potential biomarkers with varying levels of MECP2 protein. Having biomarkers that correlate with protein levels and disease severity could be a game-changer for designing and interpreting Rett clinical trials and for attracting increased biopharmaceutical interest.

RSRT has awarded $444,000 to Ciitizen, a technology company that collects, digitizes, and summarizes patient medical records, to create a comprehensive digital natural history study of Rett syndrome. Existing medical records constitute a treasure trove of untapped longitudinal data, which provides a valuable resource for biopharmaceutical companies with Rett drug development programs. This award will gather and analyze medical records for an initial cohort of 120 Rett individuals, however RSRT intends to extend beyond this cohort and collect medical records for Rett families who join RSRT’s Rett Syndrome Global Registry. The digitized medical records will be combined with parent-reported data solicited through the registry and together will create a powerful, integrated dataset that will fuel research and drug development programs.

RSRT is investing more than $186,000 in a new strategy to tackle Rett. Joseph Anderson, PhD, of the University of California Davis Medical Center, will remove hematopoietic stem cells from Rett mice, introduce a modified MECP2 gene into the cells with a lentivirus, and transplant the cells back into the mice. Some of these cells naturally migrate to the brain, where they will secrete the modified MECP2 protein to supply nearby cells. This approach has resulted in surprising and encouraging preclinical data for Angelman syndrome, another single-gene neurological disorder with similarities to Rett syndrome. A clinical trial using this type of cell therapy for Angelman syndrome is poised to begin shortly.

In 2022 RSRT will also launch the Rett Syndrome Global Registry, a virtual, caregiver-driven registry that will revolutionize what is known about Rett syndrome by bringing together previously disparate clinical data and tapping into the knowledge of Rett caregivers. The Global Registry will provide a comprehensive view of the disorder by aggregating data from caregivers, digitized medical records, patient cell lines, biosensors, and clinical trials. Access to the Global Registry will be available to the Rett community in early 2022, and caregivers will be able to centralize, track, and share data about their loved one in a clinical trial-quality database built in partnership with clinical trial database developer DSG.

“As the only organization dedicated solely to identifying and accelerating a cure for Rett syndrome, RSRT rigorously evaluates the science and funds comprehensive programs our leading scientific staff and advisors believe can work,” said RSRT CEO Monica Coenraads. “These exciting research awards would not be possible without our loyal and generous donors, and the affected families that take action and fundraise. I’m profoundly grateful to every one of them.”

RSRT bridges the divide between academic labs and biopharmaceutical companies through its prodigious scientific and business connections, and drug development experience. As a result of RSRT-led collaborations, and scientific and clinical resources funded by RSRT, today there are seven biopharmaceutical companies pursuing a cure for Rett.

LIST OF 2021 AWARDS FOR PROJECTS TO BE CONDUCTED IN 2022 AND BEYOND:

MECP2 REACTIVATION: $1,090,919
Antonio Bedalov/Kyle Fink
Fred Hutchinson Cancer Research Institute/University of California Davis
Reactivation of MECP2

CELL THERAPY: $186,254
Joseph Anderson, PhD
University of California Davis Medical Center
Feasibility of a stem cell approach for the treatment of Rett Syndrome

CLINICAL INITIATIVES: $1,394,914
Victor Faundez, PhD
Emory University
Biomarker Development - Genetic Analysis of the Rett Syndrome Cerebrospinal Fluid Proteome
$584,304

Stuart Cobb, PhD
University of Edinburgh
Biomarker Development - Genetic Analysis of the Rett Syndrome Cerebrospinal Fluid Proteome
$47,014

Ciitizen
Digital Natural History Study
$444,000

Joni N. Saby, PhD / Eric D. Marsh, MD, PhD
Children’s Hospital of Philadelphia (CHOP)
Electrophysiological (EEG) Outcome Measures for Rett Syndrome Clinical Trials
$115,906

David Lieberman, MD, PhD
Boston Children’s Hospital
Biosensor Development
$67,821

Sasha Djukic, MD, PhD
Albert Einstein College of Medicine
Support for continuing work at the Rett Syndrome Center
$25,000

Bryce Reeve, PhD
Duke University School of Medicine
Development of the Observer-Reported Communication Ability (ORCA) for Rett Syndrome
$15,294 (additional funding)

Coriell Institute
Rett Syndrome Biorepository
$53,612 (additional funding)

Harvard Stem Cell Institute
Development of patient derived induced pluripotent stem cell lines
$36,343 (additional funding)

The Jackson Laboratory
Generation and phenotypic assessment of mouse models for Rett syndrome
$5,620 (additional funding)

MECP2 DUPLICATION: $487,930
The Jackson Laboratory
Testing of siRNA compounds from Khvorova lab for MECP2 Duplication Syndrome
$362,930

Davut Pehlivan, MD
Texas Children’s Hospital
Clinical studies in MECP2 Duplication Syndrome as foundation for antisense oligonucleotide drug trials
$125,000

2021 AWARDS TOTAL: $3,160,017