The International Rett Syndrome Foundation (IRSF) has awarded nearly $2 million in Rett Syndrome Grants to seven leading researchers dedicated to uncovering the underlying pathology of Rett syndrome and identifying novel therapeutic approaches. These awards reflect IRSF’s ongoing commitment to accelerating scientific breakthroughs that will lead to new treatments and, ultimately, a cure for Rett syndrome.
“As we continue to push the boundaries of Rett syndrome research, it’s essential to support projects that explore new frontiers,” said Nupur Garg, PhD, Vice President of Research at IRSF. “IRSF provides critical early-stage funding that allows scientists to test bold ideas, refine therapeutic targets, and generate the data needed to attract further investment. Each of these awarded projects brings us closer to a future where families affected by Rett have more treatment options and greater hope for improved outcomes.”
Advancing Rett Syndrome Research Through Strategic Investment
IRSF is committed to advancing research that not only deepens our understanding of Rett syndrome but also accelerates the development of effective treatments. Our scientific strategy is built on three core pillars:
- Advancing Critical Research – Investigating the fundamental biology of Rett syndrome to unlock new treatment strategies.
- Driving Therapeutic Development – Advancing novel therapies through the treatment development pipeline.
- Ensuring Clinical Trial Success – Strengthening clinical research infrastructure to accelerate treatment availability.
“IRSF’s highly comprehensive scientific strategy ensures that we are making targeted investments at every stage of research and clinical development,” said Drew Jones, MD, MPH, MBA, Vice President of Clinical Development at IRSF. “By funding projects that deepen our understanding of Rett syndrome, advance genetic and drug-based therapies, and strengthen the clinical research network, we are working to accelerate the availability of treatments that can improve lives today while paving the way for future breakthroughs.”
IRSF offers several funding opportunities to scientists, researchers, and clinicians, including the Rett Syndrome Innovation Awards, which provide critical early-stage funding to support projects that have the potential to drive transformative breakthroughs. These awards provide seed funding for research aimed at identifying therapeutic targets and advancing treatment approaches, help advance careers in Rett syndrome research, and enable researchers to secure follow-on funding from major institutions.
“I was a graduate student studying neuroscience when I first met a girl with Rett syndrome more than 20 years ago,” said Jessica MacDonald, PhD at Syracuse University and 2024 grant recipient. “Since then, I have been driven to try and unravel the remarkable complexity of this neurological disorder. With the essential funding provided by an Innovation Award from the International Rett Syndrome Foundation, my lab is investigating novel therapeutic approaches to improve the ability of the brain to learn and adapt.”
Meet the 2024 Grant Recipients
This year’s seven awardees join a global network of researchers committed to unraveling Rett syndrome’s complexities and pioneering new therapeutic strategies. They are:
Crystal Engineer, PhD (University of Texas at Dallas)
Novel Neuromodulation Therapy to Address Sensory Hypersensitivity in Rett Syndrome
Many individuals with Rett syndrome experience extreme sensitivity to sounds and touch, as well as heightened anxiety, which can impact communication and social interactions. This study will test whether vagus nerve stimulation (VNS) paired with rehabilitation therapy can reduce sensory hypersensitivity and anxiety in a Rett syndrome rat model. VNS is already FDA-approved for epilepsy and depression and has been successfully used in PTSD treatment. If effective, this approach could offer a new therapy to improve sensory processing, social engagement, and quality of life for individuals with Rett syndrome.
Alyssa Huff, PhD
The Dysfunction of Swallow and its Coordination with Breathing in Mecp2-null Mice
Swallowing difficulties are common in Rett syndrome, often leading to choking and aspiration pneumonia, but little is known about the underlying causes. This first-of-its-kind study will use a specialized mouse model to investigate how MeCP2 mutations disrupt swallowing and its coordination with breathing. The findings will provide key insights to guide future treatments for dysphagia in Rett syndrome.
Nicoletta Landsberger, PhD (University of Milan)
Anticodon-Engineered tRNAs for the Treatment of MECP2 Nonsense Mutations
Around 30% of Rett syndrome cases are caused by nonsense mutations, which create premature stop signals that prevent the MECP2 gene from producing a full-length, functional protein. This study will test a novel approach using engineered transfer RNAs (ACE-tRNAs) to override these faulty stop signals and restore MeCP2 production. Unlike traditional gene therapy, this method works at the RNA level, potentially offering a safer and more controlled way to restore MeCP2 function. Researchers will evaluate its effectiveness in patient-derived cells and a specialized mouse model, assessing its potential as a targeted therapy for individuals with nonsense mutations in MECP2.
Jessica MacDonald, PhD (Syracuse University)
Dissecting Neurodevelopmental Disruptions in Rett Syndrome to Identify Novel Therapeutic Targets
During early development, the brain refines its neural connections, allowing for learning and adaptability. In Rett syndrome, this process is disrupted, partly due to the premature formation of perineuronal nets (PNNs)—structures that regulate brain plasticity. This study will investigate how PNNs form too early in Rett, whether astrocytes contribute to this disruption, and whether targeting these changes could help maintain flexibility in brain circuits. Understanding these mechanisms could point to new therapeutic strategies to support cognitive and developmental progress in Rett syndrome.
Sarika Peters, PhD (Vanderbilt University Medical Center)
Developing a Machine Learning Model for Sleep Classification and Autonomic Dysfunction in Rett Syndrome
Sleep disturbances are a major concern in Rett syndrome, but current methods for tracking sleep rely on caregiver reports or expensive, in-lab sleep studies. This study will use wearable sensors to monitor sleep quality, breathing disruptions (such as apnea), and biological markers linked to stress and anxiety. Researchers will develop a machine learning model to analyze these data and identify patterns related to Rett severity and behavioral outcomes. These findings could lead to improved sleep assessments, better clinical interventions, and expanded use of remote technology to support individuals with Rett syndrome.
Zhaolan (Joe) Zhou, PhD (University of Pennsylvania)
Synaptic Insights at the Protein Level in Heterozygous Female Models of Rett Syndrome
X-linked mosaicism—where some brain cells express healthy MECP2 while others do not—adds complexity to understanding how Rett syndrome presents in females. To address this cellular mosaicism, this study will use an advanced model to investigate how MeCP2 mutations alter synaptic protein composition and neuronal connectivity at the level of individual brain cells and synapses. By identifying molecular disruptions underlying the disease process, researchers aim to identify molecular targets for potential therapeutic intervention.
Xiaowei Zhuang, PhD (Harvard University)
Regulation of 3D genome organization and gene transcription by MeCP2 during brain development
MeCP2 helps organize DNA in brain cells, but how exactly that influences which genes are turned on or off is not understood. This study will use advanced imaging to examine how MeCP2 affects 3D DNA structure and gene expression over time in a Rett syndrome mouse model. Findings will address a long-standing question about MeCP2’s role in gene regulation and may help inform future treatments.
For more information about all of the research currently funded by IRSF, click here.