Integrated Validation Pipeline for Candidate Drugs for ARSACS- Dr. Bernard Brais

In Research in 2018 by ARSACS

The aims of the project are to validate candidate compounds in neurons and to combine genomics and proteomics strategies to pinpoint pathways affected by candidate drugs. Duration: One year Grant : $80,000 Contact Dr. Bernard Brais, co-director of the neuromuscular group of the Montreal Neurological Institute and Hospital 3801 University Street Montreal, Quebec, Canada H3A 2B4 Tel:(514)-398-3334; Email: bernard.brais@mcgill.ca Interesting, …

Elucidating Mechanisms Underlying Motor Coordination Rescue in a Mouse Model of ARSACS- Dr. Alanna Watt and Dr. Anne McKinney

In Research in 2018 by ARSACS

Description Aim 1 Elucidate mechanism underlying MitoQ rescue of motor coordination in Sacs-/- mice: (i)test mitochondrial dynamics and morphology using Mito-tracker administered intracellularly in Purkinje cells in treated and untreated Sacs−/− mice, (ii) test mitochondrial function using assays for mitochondrial respiration and energy consumption, and (iii) determine whether MitoQ rescues the abnormal somatodendritic localization of phosphorylated neurofilament in Sacs−/− mice.In …

Phenotyping ARSACS in Vitro Using hiPSCs Reprogrammed from Patients and Differentiated into Motor Neurons and Schwabb cells – Dr. François Berthod

In Research in 2018 by ARSACS

The objectives are to: (1) develop and characterize a 3D in vitro human model constituted of fibroblasts, motor neurons, Schwann cells and myoblasts that recapitulate the ARSACS phenotype at the motor neuron scale, (2) determine whether the ARSACS phenotype is homogeneous between different patients in vitro. Duration: one year Grant: $80,000 contact: Dr. François Berthod, professor department of Surgery Faculty …

Unbiased Sacsin Client Identification and Genetic Intervention in a Mouse Model of ARSACS- Dr. Stephen Strack

In Research in 2018 by ARSACS

This research project utilizes Sacs KO mice to answer two fundamental questions: 1) Can we leverage recent advances in quantitative proteomics to uncover early biomarkers and perhaps drivers of ARSACS pathology in the cerebellum? 2) Can genetic modulation of the mitochondrial fission/fusion equilibrium counteract cerebellar symptoms and PC degeneration? Results from this research are expected to advance our understanding of …

Unravelling Progression Biomarkers in ARSACS: a Multicenter, Transmodal Combined Fluid Biomarker and Magnetic Resonance Imaging Study – Dr. Matthis Synofzik and Dr. Roberta La Piana

In Research in 2018 by ARSACS

A combined transmodal fluid biomarker and neuroimaging study to unravel progression biomarkers for ARSACS, bringing together a unique transatlantic, multi-center consortium which will yield the by far largest , most comprehensive biomarker investigation in ARSACS worlwide, creating combined clinical, biomaterialand multimodal MRI data-sets from 125 ARSACS patients across continents. Fluid biomarker investigations will focus on neurofilaments (NFs), a particularly promissing …

Unravelling Co-Translational Quality Control of Mutant Sacsin in the ARSACS Pathogenesis – Dr. Francesca Maltecca

In Research in 2018 by ARSACS

The main objectives of this research project are to: (i) verify if a co-translational QC is the cause of sacsin absence in patients, thus uncovering the earliest step in ARSACS pathogenesis; (ii) ameliorate genotype-phenotype correlation in ARSACS by assaying residual amount of sacsin levels in a panel of patient fibroblasts carrying different mutations. The comprehension of the molecular mechanism underlying …

Caractérisation du profil clinique de la clientèle pédiatrique atteinte de l’ARSACS- Dre Cynthia Gagnon

In Research in 2018 by ARSACS

Les objectifs de ce projet sont de : 1. Documenter les atteintes motrices des membres inférieurs et supérieurs des enfants atteints d’ARSACS en termes de coordination, endurance et vitesse de marche, force des mains et sévérité de la maladie; 2. Déterminer la validité de construit des outils pour la clientèle pédiatrique atteinte d’ARSACS. Méthode Devis : Transversal multicentrique Participants : …

Development of Optimized Molecules That Reverse The Molecular Phenotype of ARSACS – Dr. Michel Bouvier

In Research in 2018 by ARSACS

The goal of this project is to develop small molecules that reverse the cellular phenotype of ARSACS into a drug that would stop the progression of the disease and/or lead to clinical improvement. The project is a multidisciplinary collaboration between Dr Bernard Brais’ (McGill Univ.) and Dr Michel Bouvier’s (IRIC, Institute of Researcher in Immunology and Cancer, Univ. of Montreal) …

Functional and Structural Studies of Sacsin Using Baculovirus Expression Systems- Dr. Kalle Gehring

In Research in 2018 by ARSACS

The central goal is to obtain pure full-length sacsin in high enough concentration for structural and functional assays. We also aim to express and study the interaction of large multidomain fragments of sacsin. These will allow us to study the structure of sacsin by X-ray crystallography and cryo-electron microscopy. Purified protein will also enable assays of sacsin chaperone function and …