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!

  Michela Fagiolini, PhD 

The Research

Dr. Fagiolini is studying how neurons in the cortex of the brain change during the onset and progression of Rett syndrome and how they change in response to Ketamine treatment. The cortex is the area of the brain that receives sensory information – sight, taste, smell, sound and touch. Rett syndrome alters the way the neurons process this sensory information.

Ketamine is a drug that has been used to treat other disorders and is being studied as a potential treatment for Rett syndrome. Dr. Fagiolini’s work will help lay the groundwork to determine proper ketamine dosing and help set parameters to evaluate ketamine’s effectiveness in Rett syndrome.

Dr. Fagiolini will image the brains of RTT mice as they respond to visual sensory information. She will compare the changes at the onset of RTT to changes after regression from RTT has begun. She will then image the brains after ketamine dosing to see its effect. This information will be used to determine the optimal dosage needed to re-establish proper function of neurons in the cortex. This work is being done on female RTT mice with a Mecp2 mutation. These mice have symptoms similar to the human condition. Because of this, Dr. Fagiolini says that the outcomes from this study will be immediately translated in the clinical setting and will help shape upcoming clinical trials.

The Hope

Dr. Fagiolini’s goal is to see how the RTT brain responds to sensory input from the environment, giving a better understanding of how abnormalities in the neuron networks of the cortex can be corrected. They will also measure the effectiveness ketamine intervention on those networks, and determine the optimal dosage needed to re-establish proper function.

This will pave the way for the development of future ketamine clinical trials and additional treatments for Rett syndrome.

The Answers to your Questions

Why is this work important to helping my child?

Our work –although conducted in our small little mouse patients - can be immediately translated into clinical settings. Indeed, clinical trials testing ketamine are in the making. This research is essential to develop proper outcome measures and proper dosing for those clinical trials.

How can Rett families help with your project?

Enrolling in the Natural History Study is the best way to help. Through the NHS, we can collect EEG and evoked potential (auditory and visual) data from those first diagnosed to those in adulthood. That information can be used to develop future clinical trials. Rett syndrome patients and their extraordinary families are our support and motivational system. We work for them to find a treatment and maybe one day a cure for these incredible children and adults with RTT.

Does the knowledge gained help treat Rett or cure Rett?

Our work will help design a more effective clinical trial that hopefully will treat Rett syndrome and significantly improve their quality of life.

What is the timeline of your work?

In December of 2019 we will have completed our study. We will share any progress made along the way with the Rett community.


The Researcher

Dr. Michela Fagiolini is an Associate Professor in the Department of Neurology at Boston Children’s Hospital, where she had launched her research on neurodevelopmental disorders and in particular Rett Syndrome. Her laboratory has an active collaboration with the Boston Rett Syndrome clinic and the laboratory of Cognitive Neuroscience.

Dr. Michela Fagiolini was awarded a Basic Research Award for the project “Two-photon imaging of excitatory/inhibitory cortical activity in mosaic Mecp2 female animal model". To better understand what is happening inside the lab, we answer some common questions about this research below.

What is two-photon imaging?

Two-photon imaging is simply a type of imaging that is ideal for visualizing the activity of distinct neurons in brain tissue of a living animal.

What does excitatory/inhibitory cortical activity mean?

In a brain and working nervous system, there are two activities required: excitation and inhibition. Excitatory signaling from one cell to the next makes the latter cell more likely to fire. Inhibitory signaling makes the latter cell less likely to fire. The balance between neural excitation and neural inhibition is crucial to healthy cognition and behavior. In Rett syndrome, it has been thought there is in an imbalance in these activities due to loss of MeCP2 protein, which regulates both brain development and maintenance. Dr. Fagiolini is looking specifically at the cortical region – the visual cortex (a part of the cerebral cortex that processes visual information).

The goal at the end of the two-year project:

Dr. Fagiolini and her lab hope to have a better understanding of how the expression or absence of MeCP2 impacts the neuronal activity of excitatory or inhibitory cortical circuits during regression and recovery in the visual cortex of RTT female mice. The experiment proposed here will allow them to directly visualize how brain cells are expressing or lacking MeCP2 change their ability to communicate and properly function during the progression of the disorder. They will also be able to understand better how pharmacological or genetic interventions affect the neurons and their ability to recover and to what degree.

For the scientific abstract of this project, click here. 




Nicholas Katsanis, PhD - Duke University 

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

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