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!

 Nicholas Katsanis, PhD - Duke University 

Using zebrafish to screen potential drugs for use in Rett syndrome. 

The Research


Dr. Katsanis will study the effects of MeCP2 using a zebrafish animal model, with the goal of developing a new, faster method to screen compounds or drugs for potential use in Rett syndrome.  This work is currently done using a mouse model.  Zebrafish have been successfully used to screen drugs for use in other diseases.  Dr. Katsanis will use zebrafish with a mutation in the mecp2 gene to test the effect of mecp2 mutation on target genes and test the effects of compounds on the zebrafish. Dr. Katsanis’s work is a first of its kind and paving the way for faster, more efficient progress in finding treatments for Rett syndrome. Click here to read more about his research.



  embryonic zebrafish

The Hope

Developing a method to screen drugs in Zebrafish could accelerate our Scout Program's drug screening capacity from 8-10 compounds per year in the mouse model to hundreds per year in zebrafish at a fraction of the cost. The mecp2 mutant zebrafish can be produced on a much larger scale than mecp2 mutant mice.  In short, we can make many more mecp2 mutant zebrafish much more quickly and at a much lower cost than mecp2 mutant mice. Dr. Katsanis aims to demonstrate that zebrafish models can accelerate the pace of screening beyond what is attainable with any other animal model. The hope is that this study will develop a more rapid and efficient screening process.

The Answers to your Questions

Why zebrafish?

Zebrafish have high similarity to many aspects of human anatomy and physiology. In the field of genetics, the zebrafish is an excellent test subject and is used in many labs to replace or to supplement higher vertebrate models, such as rats and mice, due to cost savings and time efficiency. The zebrafish is a special animal model to researchers because its’ body is transparent.  Scientists can introduce mutations that include fluorescent proteins which allow the mutation to be monitored by the “glow”. Scientists use zebrafish to study the genetic/phenotype connections associated with human disorders.

How does a zebrafish exhibit Rett-like symptoms?

Like humans, the zebrafish genome has a copy of the human gene, and its mecp2 gene can be mutated. While motor skills like hand wringing in Rett syndrome cannot be modeled in zebrafish, they do show motor defects in their swimming as early as 3 days old. We can also assess how loss of MeCP2 function affects neuronal activity, plasticity, and neural development in zebrafish. We can see dysfunction in specific neurons that are similar to those seen in Rett syndrome.

What is the cost of a zebrafish with a mecp2 gene mutation compared to a mouse?

Fractional. The biggest “savings” though is in the ability to generate very large numbers, which enable us to do studies that are simply not tenable in the mouse. Also, having a non-mammalian model is useful for animal welfare issues as well.

How does using zebrafish accelerate the screening process?

It is incredibly difficult and time-consuming to test candidate drugs in mice and you cannot test more than a handful. The zebrafish model allows us to test hundreds to thousands of candidate drugs. It also allows us to look at the whole organism and can help us study things such as metabolic effects and toxicity.

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

We are excited to demonstrate that this method can efficiently and rapidly increase the pace of drug discovery in Rett syndrome. We hope to use the zebrafish method along with the mouse and cell work currently being done to contribute to both drug discovery and drug validation.

What is the timeline of your work?

We are deeply grateful to receive two years of exploratory support from, during which time we hope to have the model validated. After that point, we should be able to move to a high throughput drug screening quickly.


The Researcher

Dr. Katsanis is Director of the Center for Human Disease Modeling at Duke University, a Professor in the Departments of Cell Biology and Pediatrics, and is the Chief Scientific Officer and Founder of drug discovery company Rescindo Therapuetics whose primary focus is on rare genetic disorders.  The Center aims to facilitate collaboration across disciplines and to develop physiologically relevant tools to study variation found in human patient genomes. As part of that effort, Dr. Katsanis leads the Taskforce for Neonatal Genomics. This multidisciplinary group of physicians and basic scientists strives to synthesize genomic and biological data for the faster diagnosis, improved/focused clinical care, and potential therapeutic paradigms, for infants and neonates with genetic conditions.

View Dr. Katsanis' full scientific abstract here. 




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

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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