Active Rett Research Funded by IRSF

More than $58 million invested in research to date

Rett syndrome is a complex disorder that requires multiple approaches. That’s why IRSF invests in innovative research both for new drugs to treat Rett syndrome AND genetic treatments for curative approaches, while also working to build a robust treatment pipeline and ensure clinical trial readiness and success.

Our strategy is simple, but powerful: improve care today and create treatments for tomorrow. We are committed to a full-spectrum approach to provide solutions for everyone living with Rett syndrome.

Scroll down to learn more about the more than 30 active research projects from around the globe funded thanks to IRSF donors and supporters. For questions or more information on our funded research, please email us.


Research INVESTIGATING GENETIC TREATMENTS AS CURATIVE APPROACHES

Vania Broccoli, PhD
Vania Broccoli, PhD
Ospedale San Raffaele S.R.L. (San Raffaele Hospital)

Modulating MeCP2 expression heterogeneity in brain cells for increasing gene therapy efficacy and safety in Rett syndrome

Current gene therapy vectors are not able to differentiate MECP2 expression between different cells. This project is designed to advance the efficacy and safety of gene therapy for moving rapidly to its exploitation in the clinical arena. A new AAV capsid and gene therapy vector with novel elements able to reduce MECP2 gene levels exclusively in glial cells will be validated.

Innovation Award, 2022

Ronald Emeson, PhD
Ronald Emeson, PhD
Vanderbilt University

RNA Editing-Mediated Modification of a Common Nonsense Mutation in Rett Syndrome

Dr. Emeson’s lab has developed a novel RNA-editing strategy to engineer short RNAs that may help efficiently repair specific mutations in the RNA transcripts encoding MECP2. Now, they will begin further study of this repair mechanism, beginning with a test tube-based system, and later followed by the use of human cell lines which have been modified to carry the MECP2 mutations.

Innovation Award, 2022

Sonia Guil, PhD
Sonia Guil, PhD
Josep Carreras Leukaemia Research Institute

Leveraging the RNA binding activity of MECP2 to improve gene replacement therapy for Rett syndrome

Dr. Guil’s lab will design a new gene therapy strategy that improves several features of the current approaches. They will explore moderating MeCP2 levels to avoid toxicity due to excessive expression of the gene (which can be as bad as its deficiency) and discriminating between cells that express the normal gene and cells that express the mutant gene.

Innovation Award, 2022

Julian Halmai, PhD
Julian Halmai, PhD
University of California, Davis

A CRISPR toolbox for curative strategies for Rett syndrome

This project employs a CRISPR-based strategy for restoring MeCP2 through X-chromosome reactivation. An improved CRISPR cassette will be designed that is dramatically reduced in size, thereby allowing it to fit well inside AAV shell for delivery into cells.

Mentor: Kyle Fink, PhD – University of California, Davis

Independence Award, 2022

Jeannie Lee, MD, PhD
Jeannie Lee, MD, PhD
Massachusetts General Hospital

Preclinical development of Rett syndrome ASO drugs

This study focuses on restoring MECP2 in patients by reactivating its dormant, normal copy carried on the inactive X chromosome via an ASO-based strategy. This will be achieved by performing proof-of-concept studies in a mouse model and optimizing preclinical candidates in patient cells.

Innovation Award, 2022

Previous Award Recipients Actively Studying Gene Therapies


Research Paving the Path to New Drugs to Treat Rett Syndrome

Sameer Bajikar, PhD
Sameer Bajikar, PhD
Baylor College of Medicine

 

Modulation of the GDF11-SMAD3 signaling pathway to treat Rett syndrome

Dr. Bajikar has found that MeCP2 could be regulating 2 key genes – GDF11 and Smad3. The imbalance MeCP2 causes within these genes may contribute to the development of Rett syndrome. With this project, he will dig deeper into restoring the proper function of these genes in mouse models and tests drugs that can restore this balance.

Mentor: Huda Zoghbi, MD – Baylor College of Medicine

Independence Award, 2022

Qiang Chang, PhD
Qiang Chang, PhD
University of Wisconsin-Madison

 

Integrated multi-level characterization of Rett syndrome disease states

Different labs study the errors that occur in Rett neurons one at a time – this makes it hard to combine the results and paint the big picture. This project studies three key changes in Rett neurons in the same neuron – permitting a holistic characterization of the disease process and providing clues about how the process can be reversed.

Co-PIs: Andre Sousa, PhD, Daifeng Wang, PhD, and Xinyu Zhao, PhD – University of Wisconsin-Madison

Innovation Award, 2022

Adam Hantman, PhD
Adam Hantman, PhD
University of North Carolina at Chapel Hill

 

Pilot study to establish abnormal motor network dynamics during reaching and grasping movements in a mouse model of Rett Syndrome

The loss of purposeful hand movements is a central feature of Rett Syndrome. This project combines large-scale neural recordings with high-resolution tracking of hand movements in animal models to advance understanding of the brain mechanisms that cause these same movements in Rett Syndrome. This may also provide valuable information about related speech or cognitive symptoms.

Innovation Award, 2022

Shixin Liu, PhD
Shixin Liu, PhD
The Rockefeller University

 

Single-Molecule Investigation of Nucleosomes as Recruiting Hotspots for MeCP2

DNA-binding is one of the fundamental roles of MeCP2 – but not all the pieces are understood. This project employs an innovative ultra-high-resolution microscopy approach, tracking one molecule of MeCP2 at a time on DNA, that could help uncover new avenues for therapeutic intervention for Rett syndrome.

Innovation Award, 2022

Yi Liu, PhD
Yi Liu, PhD
Whitehead Institute for Biomedical Research

 

The role of transcriptional condensates in Rett Syndrome

Some parts of the MeCP2 protein are flexible, and these portions help it gather together with its partners – like DNA, RNA, and other proteins – to form island-like areas within the cell’s nucleus. This project studies how RTT mutations interfere with this, and screens for drugs that can decrease or fix this defect.

Mentor: Rudolf Jaenisch, MD – Whitehead Institute for Biomedical Research

Independence Award, 2022

Lee Niswender, PhD
Lee Niswander, PhD
University of Colorado Boulder

 

Advancing an understanding of MECP2 function by identification of methylated RNA targets

MeCP2 is mainly known for its association with DNA, but researchers have started to find that it works with another key molecule – RNA. This project digs deeper into how MeCP2 works with RNA and may uncover new potential therapies for Rett syndrome.

Innovation Award, 2022

Hume Stroud, PhD
Hume Stroud, PhD
University of Texas Southwestern Medical Center

Exploring the formation and function of novel MECP2 genomic binding sites

This is a potentially paradigm-shifting study on where and how MeCP2 binds to DNA. This new exploration into the roles of previously uncharacterized mechanisms will provide more options for therapeutic strategies to treat individuals with Rett syndrome.

Innovation Award, 2022

Previous Award Recipients Actively Studying New Drugs and Therapeutics


Research ensuring clinical trial readiness and success

Tim Benke, MD, PhD
Tim Benke, MD, PhD
University of Colorado Denver

The diagnostic experience of male Rett Syndrome

Males with mutations in MECP2 have been understudied with more than 10x as many publications dedicated to females. Data from the NIH- sponsored Natural History Study suggests there is a very broad spectrum of disease symptoms and severity, some of which are different from females. This study will result in a better understanding of the diagnostic odyssey and lived experiences of parents/guardians of males with RTT in order to inform needed future clinical trials.

Co-PIs:
Dr. Talia Thompson – University of Colorado Denver
Drs. Cary Fu and Jeffrey Neul – Vanderbilt University
Drs. Amitha Ananth and Alan Percy – University of Alabama

Center of Excellence Research Award, 2022

Previous Award Recipients Actively Ensuring Clinical Trial Success


additional critical research funded by irsf

View Our Previously Funded Research