P.O. Box 50030 London, ON N6A 6H8 info@rett.ca (519) 474-6877

Canadian Research Projects

McGill University – Dr. Derek Bowie

Dr. Derek Bowie, Canada Research Chair in Receptor Pharmacology
Website: http://www.medicine.mcgill.ca/pharma/dbowielab/
Department of Pharmacology & Therapeutics,
Faculty of Medicine, McGill University
Montreal, Quebec

“The Bowie lab focuses on ionotropic glutamate receptors (iGluRs) and their role in brain development. Specifically, we are interested in understanding why there is a delay before the onset of symptoms in Rett syndrome. By identifying why there is a delay, we aim to develop a therapeutic strategy that will treat Rett syndrome kids before or soon after the onset of symptoms.”
“When it started, how long it has been going on in Canada per site?”
“The Bowie has only recently turned their attention to Rett syndrome however Dr. Bowie has been working on iGluRs for more than 15 years.”
“Our preliminary data look very promising. We hope to publish some of our work in the near future.”

Derek Bowie, B.Sc., Ph.D.,
Assistant Professor, Canada Research Chair, Tier II,
Department of Pharmacology & Therapeutics,
McIntyre Medical Sciences Building, Room 1317,
McGill University, 3655 Sir William Osler Promenade,
Montreal, QC, Canada H3G 1Y6

Email: derek.bowie@mcgill.ca
Tele: (514) 398-1581 (office); -2513 (lab)
Fax: (514) 398-6690
Web: http://www.medicine.mcgill.ca/pharma/dbowielab

University of Manitoba – Dr. Emma Frost

”My team is working at the Manitoba Institute of Child Health in
Winnipeg, Manitoba. We are investigating changes in gene expression in
a mouse model of Rett, specifically looking at the role of myelin in the
disease. My lab was started in 2005, and I have been working on Rett
since those first days (not long I realize, but we all have to start
somewhere) but my interest in Rett was started in 2002 when I was
working at Johns Hopkins in Baltimore. As for success, I like to think
that we are being very successful in our endeavours, however, we don”t
have anything published as yet. Mainly because funding agencies don”t
believe that myelin is playing a role in this disease, even though my
preliminary data indicates otherwise. And of course, funding is the
crux of all research.”


Dr. Emma E Frost
Assistant Professor
Department of Pathology,
Human Anatomy and Cell Biology &
Biochemistry and Medical Genetics
Manitoba Institute of Child Health
University of Manitoba
715 McDermot Avenue
MB R3E 3P4
(204) 789-3273 (voice)
(204) 789-3931 (fax)

Toronto Western Hospital – Dr. Eubanks

“We are doing basic neurophysiology studies in Rett models and testing prospective treatments. I have three grad students currently, and two full time technologists. I hope to expand this number in the Fall if I can find funding for another grad student.”
”All of our studies are conducted at the Toronto Western Research
Institute, which is within the Toronto Western Hospital. Our work is non-clinical; we use only mouse models of Rett syndrome. We would be classified as basic science.”
”Our interest in MeCP2 began in 1996, before it was recognized as the cause of Rett syndrome. Since 1999 our work has focused more and more on defining what is wrong in the MeCP2-deficient brain, with the hope being when we find what is wrong we can develop ways to fix it.
As for success, I suppose that is a subjective question. For the community as a whole, we have not been successful in finding a treatment or cure for Rett syndrome, although I would say we have made some progress in delivering better treatment options. If this is the ultimate determinant of whether the research has been successful, then I guess the answer has to be no.”

”However, if one considers how much progress has been made in understanding Rett syndrome, then I would argue that the success has been unparalleled over the past 5 years or so. We went from knowing a genetic cause in a protein with no known relevance in neurobiology, to opening up a whole new field – we now know epigenetic processes are critical to brain development and function. 10 years ago if you had made that statement scientists would have laughed at you. Now, there is a new field, and from Rett investigations we know a whole
lot more about how these factors function, and we are getting a better idea of what they are in the brain to do.”

”In addition, there are clinical trials underway currently using data obtained from the study of Rett models. I personally think we have been very successful at identifying the cause of Rett syndrome, and importantly, showing the condition is not irrevocable. I can not stress enough how much impact the studies showing functional improvement are, as most people in the field really did not think it
was possible to even improve the condition – much less greatly correct it. Four different labs have shown this is possible – Adrian Bird”s (Edinburgh Scotland), Huda Zoghbi (Baylor College of Medicine, Texas), Rudolph Jaenisch (Massachusetts Institute of Technology, Boston), and our work here in Toronto.”



Toronto Western Hospital
McLaughlin Pavilion
11th Floor Rm 11MC412
399 Bathurst St.
Toronto, Ontario
Canada M5T 2S8

Toronto Western Hospital – Dr. Liang Zhang

“My name is Liang Zhang, a research scientist of Toronto Western Research
Institute, and I am a neurophysiologist with expertise in examination of brain
electrical activities in rodent models. In the past several years, my lab has
worked in a close collaboration with Dr. Eubanks”s lab via using mouse models of
Rett syndrome. In addition to myself, Dr. Chiping Wu, a senior research
associate of my lab, and Jiwei He, a project student (now a PhD student of
University of Pennsylvania), play important role in our project.”

”Our research project is done in the Toronto Western Research Institute,
University Health Network. Our lab is located in the Toronto Western Hospital.”

”We use mouse models of Rett syndrome and our goals are to reveal the
pathophysiological processes that may underlies cognitive impairments and
seizures in Rett syndrome and to explore potential therapeutic manipulations.”

”We have been working on these projects since 2002.”

”Regarding neurophysiological investigation of mouse models of Rett syndrome, I
think we are in the leading position internationally, particularly regarding
examinations at cellular and macroscopic network levels”

University of Victoria – Dr. MacLeod/Dr. K. Delaney

From the Centre For Biomedical Research at the University of Victoria.
Patrick MacLeod MD Kerry Delaney PhD Davis Stuss Phd (c ). http://cbr.uvic.ca/

Our group is focusing on three areas of research that are specific to Rett Syndrome. The first, relates to the establishment of a colony of mice with the MeCP2 mutation. This has allowed a PhD candidate, Davis Stuss to perform a number of experiments that have resulted in his ability to visualize individual neurons from the brain of control animals and those with the mutation. He is developing techniques to inject fluorescent dyes into individual neurons in order to be able to measure the smallest details of the anatomy of the neurons at the level of the synapses to document the normal and abnormal development. This is an essential first step in being able to demonstrate any effect of the gene or protein replacement strategies that we are developing. Any long-term treatment strategy for the human patient with RS will require the development of a relatively non-invasive, controlled release, ethically acceptable mechanism, for introducing a normal copy of the gene or protein into the brain. These criteria are not met with currently available viral vectors that introduce the cargo using operative techniques and are also difficult to control the amount and final location of the cargo. To address this we are developing a low cost non-viral intravenous technique using what are called pegylated liposomes that have been shown to cross the blood brain barrier from the blood using a monoclonal antibody targeted to a specific receptor on neurons. Together the components act together as a “ Trojan Horse” to deliver the cargo to neurons in a controlled, low dose fashion.
The third area of research is to develop a miniature implantable, radio controlled stimulating and recording device that will allow Dr Kerry Delaney to measure several physiological factors, such as brain wave activity, breathing, heart rate and movements from a distance without having to handle the mice. This is important because, up until now most of the behavioral measurements of the treated mice have required a good deal of stressful techniques that make the results difficult to interpret. Working together we plan to develop a treatment strategy that can be documented at both the level of the neurons and behavior. If successful, this proof of concept strategy will lead to the natural development of additional cargo such as small molecules or siRNA modules for the possible treatment of RS.

P Macleod MD