Rettsyndrome.org's Current Research 

Rettsyndrome.org has, to date, invested over $44 million dollars in research. Each project below completed a rigorous peer review process that ensures the dollars are spent on projects with the highest scientific merit. In 2018 we are taking bold steps to expand our support of basic research which includes gene therapies, protein therapies, and reactivating the normal MECP2 gene on the silent X chromosome.  We also continue to support neuro-habilitation research, which is bringing effective therapies to our children now.   We feel ethically compelled to ensure that our children with Rett have the best quality of life today, while we invest in a future cure. 

 

 

Newly Funded in 2018

Basic Research Awards | Translational HeART Awards Scout Program Awards Neuro-Habilitation HeART Awards Mentored Fellowship Training Awards Clinical Research Awards

  

BDNF - human gene BDNF - human protein Bdnf - mouse gene Bdnf - mouse protein
MECP2 - human gene MeCP2 - human protein Mecp2 - mouse gene  

 

 

 

Basic Research Awards 

Rettsyndrome.org’s commitment to research that explores the biology of Rett syndrome so that we can understand what has gone wrong. 

To view the scientific abstract of the project, click on the title.


Kevin Jones, PhD - University of Colorado

Basic Research Award Amount: $150,000

 

"Testing potential regulators of BDNF expression to identify candidate Rett syndrome therapeutics"

Dr. Jones is investigating compounds that can stimulate the Brain-Neurotrophic Factor (BDNF), which enhances the function of the brain. He will be using mouse brain cells to test drugs already approved by the FDA for other uses, in order to find those that could be effective in treating Rett syndrome.  

 

 Colleen Niswender, PhD - Vanderbilt University

Basic Research Award: $150,000

 

"Tailoring gene replacement therapy for MECP2-related disorders"

Dr. Niswender is leading research to address one of the challenges of gene therapy - gene dosage issues. Dr. Niswender is working to determine whether MECP2 gene therapy will work for all mutations found in MECP2.  Many MECP2 mutations do not lead to a complete loss of protein function, which runs the risk of an overabundance of MeCP2 that can lead to symptoms of MECP2 Duplication Syndrome.

 

  Colleen Niswender, PhD - Vanderbilt University

Basic Research Award: $150,000

 

"Exploration of metabotropic glutamate receptor 3 as a target for MeCP2-related disorders" 

Dr. Niswender is studying whether metabotropic glutamate receptor 3 (mGlu3), can be a potential therapeutic target for Rett syndrome (RTT) and MECP2 Duplication Syndrome (MDS). 

   

 Kyle Fink, PhD - University of California, Davis

Basic Research Award: $150,000

 

"Programmable transcription of MeCP2 in patient iPSC-derived neurons using CRISPR/dCas9 as a putative therapeutic for Rett Syndrome"

Dr. Fink is working on a new approach in gene therapy using CRISPR/Cas9 technology.  His group is developing a method to reactivate the healthy, silenced Mecp2 gene.  Dr. Fink is a new Principal Investigator for Rettsyndrome.org.

 

Michela Fagiolini, PhD - Boston Children's Hospital

Basic Research Award: $150,000

 

"Two-photon imaging of excitatory/inhibitory cortical activity in mosaic Mecp2 female animal model"

Dr. Fagiolini is using live brain imaging of the RTT mouse model to evaluate changes in the brain directly after Ketamine treatment. This is follow-up research based on previous results.

 

 Jean-Christophe Roux, PhD - Aix Marseille

Basic Research Award: $143,000

 

 "Evaluation of AAV9-BDNF treatment in two mouse models of RTT"

Dr. Roux is researching gene therapy in mice using BDNF (Brain Derived Neurotropic Factor) instead of MECP2.  The study evaluates whether or not there can be effective treatment which bypasses MeCP2. Dr. Roux is a new Principal Investigator for Rettsyndrome.org.

 

  Lilach Sheiner, PhD - University of Glasgow

Basic Research Award: $150,000

 

 "Transgenic T. gondii as a platform for MeCP2 protein delivery to the CNS" 

Dr. Sheiner is evaluating a new way to deliver MeCP2 protein into the brain by using a parasite to deliver MeCP2This is a cutting edge approach and is being conducted on animal models.  Dr. Sheiner is located in Scotland and is a new Principal Investigator for Rettsyndrome.org.

 

Jeannie Lee, MD, PhD - Massachusetts General Hospital
Translational HeART Award: $149,996

 

"Reactivating the silent MECP2 allele through a synergistic drug mechanism" 

Dr. Lee is leading gene therapy research focused on reactivating the silent MeCP2 gene (on the inactive X-chromosome) to treat Rett syndrome.


 Translational HeART Awards
Rettsyndrome.org’s commitment to research focused on developing treatments that change the biology of Rett syndrome. HeART (Help Accelerate Rett Therapeutics) grants provide funding for early stage drug discovery and development efforts.  


Qiang Chang, PhD - University of Wisconsin - Madison

Translational HeART Award:$150,000

 

 "In Vitro and In Vivo Validation of Candidate Drugs to Treat Rett Syndrome" 

Dr. Chang will evaluate 13 potential drug candidates for Rett syndrome. He will do his research in cells and on mice. The aim of his research is not only to identify new drugs but also to create a better way to screen potential future compounds.

  


Nicholas Katsanis, PhD - Duke University
Translational HeART Award:$150,000

 

"Towards identifying therapeutic targets of MECP2 deficiency"

Dr. Katsanis is developing a new, faster drug candidate screening method using zebrafish that have a Mecp2 mutation. This method will increase our Scout Program's drug screening capacity from 8-10 compounds per year to hundreds per year and will help move potentially beneficial drug candidates into mouse model research more quickly.


Lucas Pozzo-Miller, PhD - University of Alabama, BirminghamTranslational HeART Award:$150,000

 

 "Exploring Nonsense Suppression as a Treatment for Rett Syndrome"

Dr. Pozzo-Miller is working collaboratively with Southern Research (SR) to identify compounds that best suppress the effects of MECP2 nonsense mutations (which affect approximately 35% of Rett syndrome patients). SR screened 771,345 compounds and found 157 with potential for use in Rett syndrome.  Dr. Pozzo-Miller will work with SR to determine which of those 157 are most effective.


Scout Program Awards

Rettsyndrome.org’s commitment to research that accelerates the testing of potential drugs for use in treating Rett syndrome. 


Taleen Hanania, PhD - Psychogenic, Inc

 Scout Program Award: $150,000  

 

"Drug Discovery Screen in a Mouse Model of Rett Syndrome"

Dr. Hanania is doing research on potential drug candidate compounds.  These compounds are screened in a standardized battery of tests in the RTT mouse model.  This is a unique program that increases the pace of testing, allows for potential treatments to move more quickly into clinical trials, and create partnerships with pharmaceutical and biotech companies.


Neuro-Habilitation HeART Awards

Rettsyndrome.org’s commitment to research that discovers ways to habilitate or re-train the brain through cognitive, speech, occupational and physical therapies. 


 Pamela Diener, PhD MS OTL - Georgetown UniversityNeuro-Habilitation HeART Award: $75,000

 

"Improving Upper Extremity Motor Skills in Children with RTT Using Selected Movements to Control Internet Virtual Reality Computer Games"

Dr. Diener is studying how virtual reality computer games can be used to improve upper body motor skills.  This funding will expand the number of study sites for the project to 2 sites.


 Susan Rose, PhD - Albert Einstein College of MedicineNeuro-Habilitation HeART Award:$149,912

 

 "Cognitive Outcome Measures for Rett Syndrome: Assessment of Reliability and Stability"

Dr. Rose is leading research to better understand and assess learning with eye-glaze technology.    She intends to demonstrate that they can measure memory, anticipation, and attention with eye-gaze and use those as outcome measures for clinical trials.  This is follow-up research based on previous results.


 Mentored Training Fellowship Awards

Rettsyndrome.org’s commitment to building our bench of future researchers and clinicians focused on Rett syndrome. 


 Billy Lau, PhD - University of Tennessee - Knoxville
Mentored Training Fellowship Award: $100,000

 

 "Cortical inhibitory mechanism governing auditory perception in MeCP2+/-"

Dr. Lau is studying the impact of Mecp2 mutations on the adult brain’s neural networks, gene expression and behavior.  Dr. Lau is training with Dr. Keerthi Krishnan, who was a previous Rettsyndrome.org fellow.

 


 Sarah Sinnett, PhD - University of North Carolina  Mentored Training Fellowship Award: $100,000

 

 "Can non-invasive interventions synergistically enhance the efficacy of MECP2 gene therapy?"

Dr. Sinnett is leading research to demonstrate how environmental enrichment (neuro-habilitation) can enhance the benefits of gene therapy.  The work is being done in mice.  Dr. Sinnett is training under Dr. Steven Gray, a previous Rettsyndrome.org Fellow. 

 


  Cary Fu, MD - Vanderbilt UniversityMentored Training Fellowship Award: $125,000

 

"Characterizing Biomarkers of Epileptogenesis in Rett Syndrome"

Dr. Fu is investigating seizures in Rett syndrome in a new way: by developing a predictive algorithm for RTT-related epilepsy. His group will use clinical data from the Natural History Study and use mouse models to determine characteristics that can predict seizures. Dr. Fu is training with Dr. Jeffrey Neul at Vanderbilt University.

 


Carrie Buchanan, MD - Greenwood Genetic Center

Mentored Training Fellowship Award: $125,000

 

"Behavioral Disorders in Rett Syndrome"  

Dr. Buchanan will refine clinical outcome measures using anxiety biomarkers, such as cortisol level, heart rate variability and inflammatory markers.  These measures will supplement the Rett Syndrome Behavioral Assessment measures that are currently being used in many clinical trials.  Dr. Buchanan’s goal is to improve diagnosis and treatment of anxious behaviors in RTT.  She is training with Dr. Walter Kaufmann at Greenwood Genetic Center.


 Clinical Research Awards

Rettsyndrome.org’s commitment to clinical research focused on building a national clinical trials network while conducting clinical research and trials.


 Mriganka Sur, PhD, Daniela Tropea PhD & Walter Kaufmann, PhD

Massachusetts Institute of Technology/Trinity College Dublin/ Greenwood Genetic Center

Research Contract Award: $154,550

 

"Identification of Biomarkers of IGF1’s related drugs in Rett Syndrome"

Drs. Sur, Tropea and Kaufmann are conducting international research to identify biomarkers that can predict an individual's response to either IGF1 or trofinetide. This data will be used in the protocol for the upcoming phase 3 trial of trofinetide and will be pivotal for the FDA’s approval of trofinetide.


 Daniela Brunner, PhD - Early Signal Foundation

Research Contract Award: $57,246

 

 "Wearable Sensors for Multifunctional Assessment in Rett Syndrome"

Dr.  Brunner is developing wearable, home sensor technology to measure gait, movement, heart rate, and sleep in girls with Rett syndrome. Dr. Brunner will use data from the Natural History Study to improve and expand the use of these sensors.

 

 

 

 


Previous Research Awards

Ongoing Research in 2018

The following awards were bestowed in previous years but are still very active in research in 2018.

 

Translational and Clinical Research ANGEL Awards

Rettsyndrome.org’s commitment to research focused on developing treatments that change the biology of Rett syndrome. ANGEL (Advanced Neurotherapeutic Grant of Excellence) grant awards must be comprised of very specific programs that are focused on pre-clinical drug discovery and development or clinical testing of therapeutic candidates.  



Daniel Klamer, PhD -   Anavex Life Sciences Corp.

Translational ANGEL Award:$597,886

   

 " Randomized, Double-Blind, Placebo-Controlled, Dose-Titration of ANAVEX 2-73 in Patients with Rett Syndrome "

 Anavex is a clinical-stage biopharmaceutical company developing differentiated therapeutics for the treatment of neurodevelopmental and neurodegenerative diseases. Anavex compounds target the Sigma-1 receptor, which restores homeostasis and cell function when activated. Anavex's lead compound, ANAVEX 2-73, has demonstrated good safety, bioavailability, and tolerability in Phase 1 and Phase 2 clinical trials for other indications, but more recently preclinical studies sponsored by the Rettsyndrome.org Scout Program indicated that chronic oral daily dosing of ANAVEX 2-73 demonstrated dose-related and significant improvements in an array of behavioral and gait paradigms in the RTT mouse model.


 

Jeffrey Neul, MD, PhD -  Vanderbilt University

Translational ANGEL Award:$600,000

 

 "Read-through Program for Rett Syndrome"

 

Dr. Neul is designing a platform to evaluate and screen compounds that will bypass truncation mutations in the MECP2 gene which act as a “stop sign” and prevent the production of the full-length functional protein. This platform includes both human patient derived cell lines and animal models of RTT.


 

Previous Years' Research Awards: