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

2022 Research Grant Awarded

The Ontario Rett Syndrome Association (O.R.S.A.) Board of Directors has unanimously approved the funding of one research grant totaling $50,000 from The Hope Fund for 2022. The Hope Fund has funded over $678,000 in Canadian research to date.

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.

We are pleased to award $50,000 plus indirect costs to Dr. Ellis and Dr. Zani to support their research titled: Astrocyte-derived Extracellular Vesicles to Rescue Rett Syndrome Neurons

Lay Summary:

Rett syndrome (RTT) neurons have shorter extensionscalled dendrites, and fewer synapses that interconnect neurons.RTT astrocytes are less ableto support maturation of these dendrites and synapses. Astrocytes release small dropletscalled exosomes containingmessages in the form of genetic material called microRNA.Exosomesdeliver thecargo to nearby neurons or into the bloodstream, and limitedevidence (PNAS2019) suggeststhathealthy exosomes rescueRTT neurons. However, it is not known if theexosomes are fromastrocytes, and their microRNA cargo was not examined.We willpurify exosomes from human astrocytes andtest their ability to rescue the shapeand activity of RTT neurons. First, we will produceastrocytes fromhealthy and RTT patient induced pluripotent stem cells (iPSC). Exosomes will be isolated, and theirqualitydetermined by electron microscopyandprotein markers.The microRNA cargo will be sequencedand the exosomes testedfor rescue of RTT neuron shapeand activity. We expect to findonly healthyexosomes are able to rescue, and that specificmicroRNAs are responsible. Our findings will advance the understanding of astrocyte biology,and will define a role forastrocyte microRNAs for rescuing RTT neuronsas a step towardsa potentialexosome mediatedtreatment.

James Ellis, PhD 

Hospital for Sick Children, Toronto Canada 

Dr. Ellis completed his BSc at McGill University and his PhD at the University of Toronto with Dr. Alan Bernstein developing retrovirus vectors for gene targeting. His Post-Doctoral Fellowship studying the beta-globin Locus Control Region was mentored by Dr. Frank Grosveld in London UK. Dr. Ellis established his own research team at the Hospital for Sick Children in Toronto in 1994 with a focus on gene therapy for Sickle Cell Anemia. He subsequently developed MECP2 vectors for Rett syndrome, and vectors with reporter genes that mark specific cell types. For example, the EOS vectors express specifically in pluripotent stem cells and facilitate generation of patient induced Pluripotent Stem (iPS) cells. The Ellis lab currently uses these iPS cells in collaborative research teams to model Rett syndrome, Autism Spectrum Disorders and cardiomyopathies. New research directions concentrate on post-transcriptional regulation during human neurodevelopment, and the transfer of microRNA via extracellular vesicles. Dr. Ellis is Research Integrity Advisor at the Hospital for Sick Children. 

Ellis Lab website http://lab.research.sickkids.ca/ellis/ 

Augusto Zani, MD, PhD 

Hospital for Sick Children, Toronto Canada 

Dr. Zani is a Neonatal and Paediatric Surgeon at the Hospital for Sick Children in Toronto, Associate Professor at the Department of Surgery, University of Toronto, and Scientist in the Development and Stem Cell Biology Program at the Peter Gilgan Centre for Research and Learning, SickKids, Toronto, Canada. His clinical interests are congenital anomalies and minimally invasive surgery, and his research focuses on neonatal and pediatric conditions with high morbidity and mortality rates. The Zani lab studies extracellular vesicles (EVs), which are nanoparticles released by all cells for intercellular communication. As EVs carry cargo similar to their cells of origin, EVs can be pathogenesis mediators, biomarkers of disease severity, and therapeutic agents. Among various EV-based projects, the Zani lab has recently been investigating the signatures of EVs isolated from induced plurip 

Zani Lab website: https://lab.research.sickkids.ca/zani/