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

Past Research Grants

O.R.S.A. has awarded over $500,000 in grants in the past decade. Read on for details of the exciting research projects taking place in Canada.

2019

The Ontario Rett Syndrome Association (O.R.S.A.) Board of Directors has unanimously approved the funding of two research grants totaling $150,000 from the Hope Fund for 2019. This is the largest amount approved in a single year. With this release, the Hope Fund has funded over $500,000 in Canadian research to date.

$100,000 is awarded to Dr. John Vincent and Dr. Juan Ausio. Their project, entitled Therapeutic small molecules and peptides targeting missense mutations in Rett Syndrome, hopes to find molecules that interact with mutant MECP2 proteins in such a way as to make good candidates for drug therapy. They have already received an award for free molecular design, which will be able to screen ~10 million molecules to find ones that will target specific residues within the MECP2 binding domain. They will then be able to test the successful candidate molecules to see which will reverse the molecular deficits in MECP2, paving the way for preclinical studies. Reviewers have stated that these “precision medicine approaches are at the forefront of neuroscience”.

$50,000 is awarded to Dr. James Eubanks for his project entitled A Preclinical Trial In MeCP2-Deficient Mice To Test The Repurposing Potential Of An FDA-Approved Drug For Use In Rett Syndrome. This proposal is aimed at providing symptomatic treatment to reduce the burden of mitochondrial dysfunction in Rett Syndrome, using an already-FDA-approved drug. This study is based on promising preliminary mouse data and is simple in concept and scope. It has the most immediate relevance to individuals with Rett syndrome as it is investigating the potential for a drug already in circulation to be used to ameliorate symptoms.

Grant applications were received and evaluated by O.R.S.A.’s Research Advisory Committee which is comprised of impartial and prominent neurologists, geneticists and scientists from across Canada. O.R.S.A. would like to thank all those individuals that applied for this grant.

The Hope Fund was established in 2014.The funds for this research grant were raised through donations and fundraising activities. O.R.S.A. continues to support research excellence and the development of a wide scope of Rett syndrome research across Canada.

Dr John B. Vincent completed his Ph.D. at University College London, UK, in 1994. His work included early genetic studies of autism spectrum disorders (ASD), with Profs. Hugh Gurling, Patrick Bolton and Sir Michael Rutter. After moving to Canada in 1995, he worked with Dr Jim Kennedy at the Clarke Institute of Psychiatry, then with Dr Steve Scherer at The Hospital for Sick Children, Toronto. Since 2002, he has worked as a Senior Scientist at CAMH, and Professor, Dept. of Psychiatry, University of Toronto, and cross-appointed as a full member in the Institute of Medical Science at the University of Toronto. His work is mainly on the genetics of neurodevelopmental disorders, including Rett syndrome, focussing on X-linked genes such as MECP2 and PTCHD1, as well as identifying many new autosomal recessive genes through studying consanguineous families. Many of the genes discovered have since become integrated in standard genetic diagnostic testing gene panels. In 2004, he co-authored a seminal paper on the identification of an alternative version (isoform) of the Rett syndrome protein, MeCP2, and identifying the first Rett mutation in MECP2 exon 1, with the implication that this new version is the relevant isoform for Rett syndrome (Mnatzakanian et al, 2004). This has since been shown by numerous studies to be correct (e.g. Yasui et al, 2014). Dr Vincent’s group also identified the gene PTCHD1 as a new X-linked gene for ASD (Marshall et al, 2008; Noor et al, 2010; Chaudhry et al, 2015; Ung et al, 2018). Dr Vincent has published over 150 peer-reviewed research papers, including 11 on Rett syndrome and MECP2.

Dr. Juan Ausió, Ph.D., is a Professor in the Department of Biochemistry and Microbiology at the University of Victoria, BC, Canada. He received his B. Sc. from the University of Barcelona, Catalonia, (Spain). He received a M.Sc. and a Ph. D. from the University of Barcelona, Catalonia, (Spain) in 1976 and 1980, respectively. He was a postdoctoral fellow at the Polymer Department at the Weizmann Institute of Science, Israel, from 1981-1984 and at the Department. of Biochemistry and Biophysics, Oregon State University, Corvallis, OR, USA from 1984-1986. From 1986-1988 he became a Senior Research Associate at Dept. of Biochemistry and Biophysics, Oregon State University, Corvallis, OR, USA. In 1988-1989 he was appointed Colaborador Cientifico at the Spanish Research Council at the Centro de Investigación y Desarrollo Consejo Superior de Investigaciones Cientificas, Barcelona, Catalonia, Spain. He has been a Faculty member of the Department of Biochemistry and Microbiology at the University of Victoria since January 1990, where he is currently a full Professor. Dr. Juan Ausió’s research interests focus on structural characterization of biological macromolecular assemblies, and nuclear proteins with special emphasis on chromosomal protein-DNA interactions. Current research includes studies on methyl CpG binding protein 2 (MeCP2) and its role in the modulation of neural cell chromatin organization and function with special emphasis on the alterations arising from Rett-syndrome-related MeCP2 mutations. Dr. Ausió has been the co-organizer of several European Rett syndrome meetings: The First International meeting of the Spanish Association of Rett Syndrome (AESR) in Spain (July 2017) and “Rett syndrome research, towards the future” in Italy (September 2018).

Dr. Eubanks is a neurobiologist at the Krembil Research Institute in Toronto, Canada – the home of the world champion Toronto Raptors. Dr. Eubanks came to Toronto in 1992, and started his own independent laboratory in 1994. The focus of his work at that time focused on defining how epigenetic factors influence the sensitivity of the brain to epilepsy and stroke. In the early 90’s, MeCP2 was one of a relatively small number of epigenetic factors that had been identified, which is why his group was examining MeCP2 before its role in Rett syndrome was revealed. With the identification in 1999 that MECP2 mutations cause Rett syndrome, his interests shifted towards delineating how MeCP2 normally regulates brain development and function, and to identifying how the absence of MeCP2 affects brain activity. By identifying deficits caused by MeCP2 dysfunction, his work has identified targets for rationale drug development programs working to develop Rett syndrome treatments. The first clinical trial based on his research has now received approval from Health Canada and will soon begin. Dr. Eubanks conducted his training in the United States, where he received a bachelor’s degree from the University of California, Davis, and a PhD degree from the University of California, San Diego. Upon completion of his Doctoral degree, he then conducted postdoctoral training at the Salk Institute and at Duke University before coming to Toronto. He is currently a Senior Scientist and Division Head at the Krembil Research Institute in Toronto, and a Professor at the University of Toronto. He is member of the Scientific Advisory Board for the Ontario Rett Syndrome Association, the International Rett Syndrome Foundation, and the University of Toronto Epilepsy Research Program. His lab is currently funded by the Canadian Institutes of Health Research, the Ontario Brain Institute, the LouLou Foundation, and the National Institutes of Health.

The Ontario Rett Syndrome Association (O.R.S.A.) is a volunteer, not-for-profit charity for parents, caregivers, researchers, medical professionals and other interested support agencies and individuals. O.R.S.A. became incorporated in 1991. Its Board of Directors is comprised of parents and caring citizens. Support is provided to families regionally. The association funds Canadian research projects, three Rett Syndrome Clinics, bi-annual conferences and developed the Canadian Rett Syndrome Registry. O.R.S.A. advocates to the needs of individuals with Rett syndrome and their families provincially and nationally.

2018

The Ontario Rett Syndrome Association (O.R.S.A.) Board of Directors has unanimously approved the funding of two $25,000 Research Grants from the Hope Fund for 2018. This is the fourth year in a row that the Hope Fund has awarded grants totaling $250,000!

The first $25,000 grant was awarded to Dr Mojgan Rastegar from the University of Manitoba. Dr Mojgan Rastegar plans to further study the role of metformin (a current and commonly available drug, used most frequently in the treatment in diabetes) as a potential therapeutic agent in the treatment of Rett Syndrome. Metformin is thought to possibly stimulate the key system that is underactive in Rett Syndrome. There is already a considerable amount of preliminary data to support this line of reasoning. This study aims to help take this “to the next level”. Dr Rastegar has been a prominent Rett Syndrome researcher for a number of years, and is a past grant winner who has shown passion, dedication, and persistence toward Rett research.

The second $25,000 grant was awarded to Dr Kerry Delaney to study neural connectivity in mosaic brain tissues using newer optogenetic techniques, hoping to shed further light on the clinical implications of the real-world heterozygosity in female Rett syndrome brains. It is hoped that this preliminary study may lay the foundation for future studies and for larger CIHR grant applications. It also will help to bring new researchers into the Rett field. One reviewer has described this proposal as being “at the cutting edge of technology, and addresses an area that until now has remained untouchable”.

These applications were received and evaluated by O.R.S.A.’s Research Advisory Committee that comprised impartial and prominent neurologists, geneticists and scientists from across Canada.

2017

London Ontario – May 5, 2017 – The Ontario Rett Syndrome Association (O.R.S.A.) Board of Directors has unanimously approved the funding of a $100,000 Research Grant to Dr. David Grynspan (Pediatric Pathologist, Children’s Hospital of Eastern Ontario, Ottawa, ON). The study is entitled “Treatment Strategies for Gastrointestinal Dysfunction in Rett Syndrome” and Dr. Grynspan’s collaborators for this work include Professor William Staines of the University of Ottawa and Dr. Sarah Schock, Research Associate at the CHEO Research Institute. This application was one of several received and evaluated by O.R.S.A.’s Research Advisory Committee that comprised of prominent neurologists, geneticists and scientists from across Canada.

This study aims to identify drugs able to restore normal intestinal function in Rett mice. The goal is that this would lead to effective drug therapy for intestinal dysmotility in Rett humans, and perhaps help to develop therapies for reversing neuronal connectivity problems in Rett brains. It is a rather novel approach in that this study plans to evaluate the enteric (ie- gut) nervous system, rather than directly studying the central nervous system as in most other studies. It is felt that this study, given its novel approach and its focus on a very common area of clinical concern, would be of scientific value to the research community at large as well as of great interest to the families most directly supported by O.R.S.A.

The Hope Fund was established in 2014. This is the third grant being released from this fund and the largest grant released by O.R.S.A. to date. The funds for this research grant were raised through donations and fundraising activities. O.R.S.A. continues to support research excellence and the development of a wide scope of Rett syndrome research across Canada.

2016

London, Ontario – April 29, 2016 – The Ontario Rett Syndrome Association (O.R.S.A.) Board of Directors has unanimously approved the funding of two $25,000 Research Grants from The Hope Fund.  The Hope Fund was established in 2014 and this is the second year that grants have been released from this fund.  The funds for these research grant were raised through donations and fundraising activities.  O.R.S.A. continues to support research excellence and the development of a wide scope of Rett syndrome research across Canada.

The first $25,000 grant was awarded to Dr. James Eubanks from Toronto Western Hospital with an application entitled “Testing new read-through drugs for prospective treatment of Rett Syndrome”. Testing new read-through drugs for prospective treatment of Rett Syndrome”. This study aims to evaluate the potential for newer drugs to overcome certain genetic mutations found in Rett Syndrome, in turn leading to production of a normal MeCP2 protein. This could potentially lead to further studies geared toward larger therapeutic development. This study has been peer-reviewed by 3 separate and unbiased reviewers and has been unanimously endorsed as highly relevant and very feasible.

The second $25,000 grant was awarded to Dr Mojgan Rastegar from the University of Manitoba. Her study is entitled “MeCP2 mutation and Rett Syndrome; Investigating the brain-specific molecular signature of murine and human RTT brain”.  These applications were received and evaluated by O.R.S.A.’s Research Advisory Committee that comprised impartial and prominent neurologists, geneticists and scientists from across Canada.  This study aims to evaluate the potential differences in male vs female brains (both mouse and human) with Rett Syndrome mutations. The rationale for this is that most people with Rett Syndrome are female, yet many of the studies to date have been conducted on male mouse models. Dr. Rastegar aims to evaluate if there are significant differences here and if this needs to be further evaluated for future planned studies.

2015

London, Ontario – March 27, 2015 – The Ontario Rett Syndrome Association (O.R.S.A.) Board of Directors has unanimously approved the funding of a $50,000 Research Grant to a joint grant application from Dr. Juan Ausio (Biochemistry and Microbiology, University of Victoria, BC) and Dr. John Vincent (Neurogenetics, University of Toronto).

Their application was one of several received and evaluated by O.R.S.A.’s Research Advisory Committee that comprised of prominent neurologists, geneticists and scientists from across Canada. It is entitled “Translational correlation of MeCP2 chromatin alterations in male and female missense mutations” and is a collaboration between two world-renowned investigators, with concise and achievable objectives.

The project revolves around the study of specific identified mutations in Rett syndrome (RTT) and aims to further the understanding of the pathogenesis of RTT and develop new insights into the factors affecting clinical phenotypes in RTT. DNA is the molecule responsible for the storage, retrieval and replication of the genetic material. In the nucleus of the cell, DNA interacts with proteins known as histones and the resulting association is called chromatin. In the brain, an additional highly abundant chromatin protein, MeCP2, is present that binds preferentially to methylated regions of DNA. Mutations of MeCP2 cause an impairment of the binding of this protein to DNA and hence to chromatin. Such alterations result in the Rett syndrome neurodevelopmental disease. Mutations of MeCP2 across the entire MeCP2 molecule are deleterious to different extents, all of them leading to Rett cases with different degrees of severity. However, neither the reason for this, nor the alterations of chromatin responsible, nor their relation to the extent of severity of the Rett syndrome outcomes are clearly understood. The idea behind this project is to combine the expertise of two well established groups in Canada working on MeCP2 and Rett syndrome to address such questions for two novel mutations of MeCP2:( Ala2Val) identified in three girls with classic Rett syndrome), and (Prol 52His) affecting the methyl binding domain (MBD)I, identified in an adult male with intellectual disability with additional comorbid features. This could potentially lead to further future studies aimed at discovering newer drug therapies.

The Hope Fund was established in 2014. This is the first grant being released from this fund and the largest grant released by O.R.S.A. to date. The funds for this research grant were raised through donations and fundraising activities. O.R.S.A. continues to support research excellence and the development of a wide scope of Rett syndrome research across Canada.

2012

The board of O.R.S.A. unanimously approved the funding of up to $25,000.00 to sponsor the second Canadian Rett Syndrome Research Scientific meeting held on Thursday, April 26th, 2012.  Over twenty-five researchers from across Canada came together at the Delta Meadowvale Hotel to meet each other, to share their RTT research project and to generate future research collaborations.  In 2006 the first Canadian Rett Syndrome Research meeting was held in Vancouver, BC.  O.R.S.A. provided funds towards the 2006 meeting. As expected the 2012 scientific meeting was a huge success. The difference from the 2006 meeting is there are over double the amount of researchers attending.  Rett syndrome research in Canada is expanding rapidly. Findings from Canadian research projects are providing vital information to the world wide research community. O.R.S.A. is proud to fund and host this event and to support Canadian Rett syndrome research.

2011

London, Ontario – July 25, 2011 – The Ontario Rett Syndrome Association Board of Directors has unanimously approved the funding of a $25,000 Research Grant to Dr. Yaron Finkelstein, Associate Professor of Pediatrics, Pharmacology and Toxicology at the University of Toronto and staff physician at The Hospital for Sick Children, Toronto.

 

Dr. Finkelstein’s research grant proposal submission, entitled Dose-Response Efficacy and Safety Analysis of Recombinant Human IGF-1 in Girls with Rett Syndrome, was evaluated by O.R.S.A.’s Research Advisory Committee. This committee is comprised of prominent neurologists, geneticists and scientists from across Canada assisted by members of O.R.S.A.’s Board of Directors.  Dr. Finkelstein’s project is a collaborative venture with Boston Children’s Hospital. Additional investigators involved include Matt Gregas, PhD, Ingrid Holm, MD, MPH, Omar Khwaja, MD, PhD, Leonard Rappaport, MD and Mriganka Sur, PhD.

2010

London, Ontario  – September 20, 2010 – The Ontario Rett Syndrome Association Board of Directors has unanimously approved the funding of a $35,000 Research Grant to Dr. John J. Greer, PhD, AHFMR Scientist and Professor, Department of Physiology at the University of Alberta.

 

Dr. Greer’s research grant proposal submission, entitled Investigation of Respiratory Dysfunction in a Mouse, was evaluated by O.R.S.A.’s Research Advisory Committee. This committee is comprised of prominent neurologists, geneticists and scientists from across Canada assisted by members of O.R.S.A.’s Board of Directors.  Dr. Greer’s project collaborators include Jun Ren, Postdoctoral Fellow and Wei Zhang, Research Associate.