has a cutting edge research line -up this year. Our passionate, dedicated scientists are attacking Rett syndrome from every angle with a scope that includes gene therapy,  CRISPR technology, pharmaceuticals, wearable devices and neuro-habilitation. Their work is the source of our HOPE.   Join us in this series to meet our researchers and share our excitement!

Colleen Niswender, PhD and Rocco Gogiliotti, PhD, Vanderbilt University

Recipient of a $150,000 Basic Research Award for this work


"Tailoring gene replacement therapy for MECP2-related disorders"


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


The Research

Drs. Niswender and Gogliotti are leading research to address one of the most important challenges of gene therapy - gene dosage.  The MECP2gene controls how much MeCP2 protein is made in the body.  When there is a mutation in the MECP2gene, protein levels and protein function are affected, causing many of the symptoms associated with Rett syndrome and similar disorders.  However, across the spectrum of Rett patients, there are a number of patient-relevant mutations that may not induce equivalent impact on MeCP2 levels or function.

One of the difficulties with gene therapy is determining how much of the gene needs to be delivered to patients to obtain the correct level of the MeCP2 protein. Too little protein may not improve symptoms and too much protein can lead to symptoms of MECP2 Duplication Syndrome.  Drs. Niswender and Gogliotti are working to evaluate the effectiveness of gene therapy for different MECP2mutations and also testing whether increasing MeCP2 levels on top of specific point mutations may put some patients at increased risk for MECP2 Duplication-like symptoms. Click HERE to read more about their research.


The Hope

Determining the correct dosing levels for effective gene therapy across a range of Rett models is an important next step in development of this therapeutic strategy.  Drs. Niswender and Gogliotti will be able to conduct these delicate studies on mice that have mutations that mirror human mutations.  This will allow them to study the effects of gene dosage and function, and the effects of expressing normal MeCP2 protein in the presence of several different patient-relevant mutations.


The Answers to Your Questions

What is the most exciting/hopeful aspect of this project and its possible results?

One important result from this work will be an understanding of the predicted efficacy and safety of MeCP2-replacement strategies across a range of mutations. We believe that developing an understanding of how disease-relevant mutations impact these factors will be complimentary to existing datasets in knockout mice, and will provide answers to questions that are critical to advancing gene therapy into Rett syndrome patients.

Why is this work important to helping my child?

Gene therapy trials are, excitingly, becoming a reality for Rett syndrome patients. A comprehensive understanding how this approach affects mice mimicking each patient populations will help develop a rational approach for these first trials, and allow for the rapid translation of early results across the spectrum of Rett syndrome patients.

What are you looking for/measuring/trying to solve in simple terms?

This particular grant is asking the following questions relevant to gene therapy: 1) will increasing MeCP2 expression work equally in the context of specific mutations, and 2) are some patients at elevated risk for MECP2 Duplication-like side effects based on their unique mutation.

Is there any way for families to help with your project? 

Participation the Rett syndrome Natural History Studyis one important way that families can help with our research. As we advance new therapeutics into clinical trials, we need to ensure that we are able to examine and quantify outcome measures to test if a drug candidate or therapeutic approach like gene therapy is working. The more we can understand about Rett syndrome patients across a whole spectrum of mutations, the better we can plan for a clinical trial. For example, perhaps patients with one mutation exhibit more severe symptoms in a specific disease domain, like apneas or seizures, than patients with a different mutation. This will assist in interpreting data in eventual trials, where one patient may respond better than another.

Does the knowledge gained help treat Rett or cure Rett?

Gene therapy, if successful, is predicted to be a curative strategy for Rett syndrome. The more information we can obtain about potential responsiveness or safety of gene therapy based on specific mutations, the better we can plan for expanded trials if warranted by early data.



The Researchers

Dr. Colleen Niswender is a Professor of Pharmacology and Director of Molecular Pharmacology at the Vanderbilt Center for Neuroscience Drug Discovery (VCNDD) in Nashville, TN. She has established a research program around the therapeutic potential of metabotropic glutamate and muscarinic receptors in Rett syndrome and MeCP2-related disorders.  VCNDD’s “Team MeCP2” is focused on the study of MeCP2-related disorders with a goal toward new therapeutics development for these and other neurodevelopmental and psychiatric disorders. Excitingly, the VCNDD has now advanced a compound into a clinical trial; this compound is designed to treat cognitive impairments in schizophrenia and Alzheimer’s disease.

Dr. Rocco Gogliotti joined the Vanderbilt Center for Neuroscience Drug Discovery (VCNDD) in April of 2012 as a post-doctoral fellow and joined the Vanderbilt Department of Pharmacology as an Assistant Professor in October of 2017.  Rocco’s work in the VNCDD has focused on the syndromic forms of autism, such as Rett syndrome and MECP2-Duplication syndrome. Through a combination of genetic, behavioral and pharmacological methodologies, he seeks to better understand the disparities in nervous system function during health and disease, and to design novel intervention strategies to correct these deficits.


In Their Own Words


 To see their complete scientific abstract, click HERE.





Daniela Brunner, PhD, Early Signal Foundation 

Jean-Christophe Roux, PhD, Inserm UMR 1251, Marseille Medical School

Susan A. Rose, PhD, Albert Einstein College of Medicine

Kyle Fink, PhD, University of California- Davis

Colleen Niswender, PhD – Vanderbilt University  

Dr. Jenny Downs, Telethon Kids Institute in Australia 

John M. Bissonnette, MD of Oregon Health and Science University

Carla J. Shatz, PhD of Stanford University

Keerthi Krishnan, PhD of Cold Spring Harbor Laboratory

Omar Khwaja, MD, PhD, MCRP of Children’s Hospital Boston

Rajiv R. Ratan, MD, PhD of Winifred Masterson Burke Medical Research Institute, Weill Medical College of Cornell

Lisa Monteggia, PhD, University of Texas Southwestern Medical Center

Zhaolan “Joe” Zhou, PhD, University of Pennsylvania, School of Medicine

Monica J. Justice, PhD, Baylor College of Medicine

Yi Eve Sun, PhD, University of California, Los Angeles

Liang Zhang, MD, PhD, University Health Network, Toronto Western Research Institute

John Christodoulou, AM, MB, BS, PhD, FRACP, FFSc, FRCPA, CGHGSA, Children’s Hospital at Westmead, Sydney, Australia

Aleksandra Djukic, MD, PhD, Tri-State Rett Syndrome Center, Montefiore Medical Center, Albert Einstein College of Medicine

Steven Gray, PhD, University of North Carolina at Chapel Hill

Investigator Spotlight: Qiang Chang, PhD, University of Wisconsin-Madison

Jeffrey Neul, MD PhD, Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital and Baylor College of Medicine

Huda Y. Zoghbi, MD, Howard Hughes Medical Institute, Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital and Baylor College of Medicine

Gail Mandel, PhD, Howard Hughes Medical Institute, Vollum Institute, Oregon Health and Science University