Research
Strategy
Ataxia Charlevoix-Saguenay Foundation
In 2006, the Foundation was created and funded the first research to be undertaken since the identification of the Ataxia gene in 2000. It was crucial to begin research in order to discover a treatment for Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS).
Since its creation, the Foundation has funded several research projects related to this neurological disorder. The Foundation is a charitable organization with no employees and is supported entirely by private donations and volunteers who support the cause. The total administration costs are less than 2% of the funds raised which allow almost all the funds to be totally dedicated to research.
Research Objectives
The main research objective of the Ataxia Charlevoix-Saguenay Foundation is to develop a treatment for ARSACS. Every year the Foundation financed several research projects in Canada and abroad. The efforts of the Foundation are concentrated currently in three main research areas:
Research Grants
To further encourage and accelerate the development of a treatment for ARSACS, the Foundation provides grants and opportunities to researchers.The research grant could be as high as $100,000 for a 12 month period and could be renewed for a second year. It should be noted that the grant funding from the Foundation cannot be used to cover indirect costs. See Financing Offer , and ARSACS Appendix
Scientific Advisory Board
All applications for research grants are evaluated by the Scientific Advisory Board of the Ataxia of Charlevoix-Saguenay Foundation according to specific criteria.
Current ARSACS Research Projects for 2021-2022
“Charting the neurodevelopmental stage of ARSACS (NeurodevARSACS): A cross-species longitudinal characterization of the early molecular changes in the brain, CSF and blood” – Drs. Justin Wolter, Matthis Synofzik & David Mengel
It is well established in neurodegenerative diseases that early therapeutic intervention - ideally before neurodegenerative cascades begin to breakdown neuronal function - is key to the success of disease-modifying therapies. Yet we do not understand the early...
“Unravelling defective Purkinje cell-postsynaptic signalling in ARSACS” – Dr. Francesca Maltecca
We discovered that sacsin specifically localizes at the post-synaptic density of the cerebellum, where it controls key proteins involved in synapse organization and trans-synaptic signaling, required for tuning the firing properties of Purkinje cells. The project aims...
“Structural Determination and Super Resolution Imaging of Sacsin” – Dr. Walid Houry
The SACS protein, whose mutation results in ARSACS, is among the largest proteins in human cells (4579 residues), which hindered the determination of its structure and made basic biochemical experiments problematic. In the proposed project, we aim to use novel tagging...
“Preclinical studies in the Sacs KO mouse model of ARSACS”- Dr. Stefan Strack
The Strack team at the University of Iowa plans to continue with preclinical studies to prevent or reverse ARSACS symptoms in the SACS knock-out mouse model. Specifically, they are hoping to improve mitochondrial function via gene therapy and electromagnetic fields....
“Évaluer l’efficacité d’un programme de réadaptation à domicile visant l’amélioration des atteintes motrices, de l’équilibre, de la mobilité, des chutes et des activités courantes chez les personnes atteintes d’ARSACS” – Dre Elise Duchesne
L’ataxie récessive spastique de Charlevoix-Saguenay (ARSACS) est une maladie incurable caractérisée par plusieurs déficiences motrices progressives apparaissant dès l’enfance. Bien que les atteintes soient majeures, entraînant de grandes difficultés à marcher...
“Is ARSACS a Tauopathy?”- Dr. Paul Chapple
This is the continuation of the project. More specific details to come. As an indication of the research, following is the description of last year work. Currently we are looking carefully at sacsin’s interaction with cytoskeletal proteins and...
“Exploring the role of genetic and epigenetic modifiers in modifiers in ARSACS” – Dr. Daniele Galatolo
The overall aim of this research is to identify the potential co-occurrence of genomic variants beyond mutations in the SACS gene and the epigenetic effects that might explain the different phenotype severity existing among ARSACS patients. Grant: $52,000 Duration :...
“Therapeutic Approaches for ARSACS”- Drs. Benoit Gentil and Heather Durham
ARSACS is characterised by the lack of sacsin expression and the formation of intermediate filaments bundles in neurons and fibroblasts derived from skin biopsies. Our strategy over the last years has been aimed at developing a replacement therapy, by peptide and/or...
“Elucidating mechanisms underlying motor coordination rescue in a mouse model of ARSACS” – Drs. Alanna Watt & Anne McKinney
One of the hallmark features of ARSACS is dysfunction and eventual death of Purkinje cells in the cerebellum, which contributes to ataxia. Strikingly, not all Purkinje cells become ill and die: rather, there are specific patterns of vulnerability and resilience to...
Partnerships
The Ataxia Charlevoix-Saguenay Foundation is always looking for opportunities to work in partnership with other organizations and pharmaceutical companies to further the understanding of this disease and conduct independent research.
PROSPAX Project
The Ataxia Charlevoix-Saguenay Foundation is one of the 3 patient advocacy organisations participating in the PROgression chart of SPAstic ataXias (PROSPAX) research project. PROPSPAX, a 3 year project launched in September 2020, is a novel collaborative effort between several neurologists across Canada and Europe.
It is an unique opportunity for patients to have their voice heard by researchers, to make sure that the questions they are trying to answer are the ones that are important to a person living with the condition. The PROSPAX project will focus on two conditions – ARSACS and SPG7.
TREAT-ARCA Project
The Foundation is pleased to represent the ARSACS patients on the research project “Designing a toolbox of paradigmatic treatments for a targeted molecular medicine approach to autosomal-recessive ataxias”. The project has received funding from the European Union’s Horizon 2020 research and innovation programme under the European Joint Program Rare Disease.
The specific objective is the pre-clinical-research to develop effective therapies for rare diseases. It aims at designing and testing new complementary treatment strategies, including both repurposed and newly identified molecules, as well as gene therapies in two exemplary multisystemic flagship ARCAS: Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) and COQ8A-ataxia (ARCA2). It is a 3 year project.
Critical Path to Therapeutics for the Ataxias consortium project
The Foundation is a member of the Critical Path to Therapeutics for the Ataxias (CPTA) consortium as a patient advocacy group.
The consortium, launched in February 2021, is a public-private partnership focused on optimizing clinical trials for inherited ataxias. It involves the participation of government regulatory and research agencies, academia, patient organizations, and bio-pharmaceutical companies.
C-Path is an independent nonprofit organization created to improve the drug development process.
Preclinical and Clinical Trials
The Foundation is ready to conduct preclinical and clinical trials. It has the expertise and the tools available. Furthermore, the existing International ARSACS Patient Registry is a good source of potential patients interested in participating in such a trial.
Research tools available
Sacs Knock Out mouse (# 033221)
Sacs Knock In R272C mouse (# 033385)
Two iPS cell lines are available for research, 1 female and 1male. These cells are derived from samples taken from people diagnosed with ARSACS (both are homozygous c.8844delT). They have been generated by the Sendai virus method.
CONFERENCES
2021 Neuroscience annual meeting, Sept 28-30, 2021
The Critical Path Institute 2021 Neuroscience annual meeting will be held on September 28-30, 2021 in Washington, DC. A representative of the Foundation will be attending as a member of the Critical Path to Therapeutics for the Ataxias (CPTA) consortium.
International ARSACS Symposium Nov 4, 2021
The 6th International ARSACS Symposium will be held on November 4,2021 for the latest research updates on ARSACS or related topics to ARSACS. The keynote speaker will be Dr. Jeremy Schmahmann from the Massachusetts General Hospital. Half-day virtual conferences, free registration, opened to all. Register now.
Joint conference Symposium ARSACS and SRCA, May 18-19, 2023
Unique opportunity: ARSACS Symposium and the Society for Research on the Cerebellum and Ataxias (SRCA) for a joint confeence to be held in Quebec city on May 18-19, 2023. Details to come.
Publications on ARSACS
October 21, 2021 - “Functional mobility in walking adult population with ataxia Charlevoix-Saguenay”
“Functional mobility in walking adult population with ataxia Charlevoix-Saguenay” Research done by Dr C. Gagnon and her team published in Orphanet Journal of Rare Diseases. First study to focus on adult walkers with ARSACS.
October 16, 2021 -"Assessment of sacsin turnover in ARSACS patients: implications for molecular diagnosis and pathogenesis”
“Assessment of sacsin turnover in ARSACS patients: implications for molecular diagnosis and pathogenesis” Dr. Maltecca and her team’s research paper published in Neurology.
September 9, 2021 -"The ataxia protein sacsin is required for integrin trafficking and synaptic organization"
“The ataxia protein sacsin is required for integrin traficcking and synaptic organisation” article submitted for publication by ARSACS researchers.
February, 2021 -"Ciliary Ganglioplegic Migraine Associated with SACS Mutation"
“Ciliary Ganglioplegic Migraine Associated with SACS Mutation” article published by researchers from Republic of Korea in Journal of Ophtalmology and Visual Sciences
February 19, 2021 -"From fuziness to precision medicine : on the rapidly evolving proteomics with implications in mitochondrial connectivity to rare human disease"
December 23, 2020 - "Docosahexaenoic acid in ARSACS: observations in 2 patients"
“Docosahexaenoic acid in ARSACS: observations in 2 patients” published in BMC Neurology. The article does not necessarily reflect the views and positions of the Foundation. It engages solely the author.
December 22, 2020 - "Case Report: Expanding the Genetic and Phenotypic Spectrum of Autosomal Recessive Spatic Ataxia of Charlevoix-Saguenay""
ARSACS_in_Iran_case_report article published in Frontiers in Genetics.
December 17, 2020 - "The importance of balancing Sacsin protein levels in ARSACS"
“The importance of balancing Sacsin protein levels in ARSACS” article published in SCA Source.
October 13, 2020 - An excellent source of information on ARSACS published in the GeneReviews
An excellent source of information on ARSACS published in the GeneReviews. GeneReviews is an online database containing peer-reviewed articles that describe specific diseases.
February 14, 2020 - "A new measuring stick for ARSACS"
“A new measuring stick for ARSACS” by Dr. Cynthia Gagnon published in the SCA Source.
October 23, 2018 - “Sacsin, mutated in ataxia ARSACS, regulates intermediate filament assembly and dynamics”
“Sacsin, mutated in ataxia ARSACS, regulates intermediate filament assembly and dynamics” by Dr. Benoit Gentil published in the Federation of American Societies for Experimental Biology Journal (FASEBJ).
September 19, 2018 - "From motor performance to participation: a quantitative descriptive study in adults with autosomal recessive spastic ataxia of Charlevoix-Saguenay"
“From motor performance to participation: a quantitative descriptive study in adults with autosomal recessive spastic ataxia of Charlevoix-Saguenay“, Dr Cynthia Gagnon, Orphanet Journal of Rare Diseases.
August 29, 2018 - "An exploratory natural history of ataxia of Charlevoix-Saguenay"
“An exploratory natural history of ataxia of Charlevoix-Saguenay“, Dr Cynthia Gagnon, American Academy of Neurology.
June 21, 2018 - "Altered synaptic and firing properties of cerebellar Purkinje cells in a mouse model of ARSACS"
“Altered synaptic and firing properties of cerebellar Purkinje cells in a mouse model of ARSACS“, Dr Anne McKinney and Dr Alanna Watt, The Journal of Physiology.
May 29, 2017 - A research paper looking at the cytoskeleton in cells cultured from ARSACS patients
A research paper by Dr. Paul Chapple published in the Human Molecular Genetics journal looking at the cytoskeleton in cells cultured from ARSACS patients.
List of publications from 1979 to January 19, 2019
List of publications on ARSACS from 1979 to January 19,2019