by ARSACS | Aug 23, 2018 | Research in 2018
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...
by ARSACS | Jul 27, 2018 | Research in 2018
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...
by ARSACS | Jul 27, 2018 | Research in 2018
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...
by ARSACS | Jul 27, 2018 | Research in 2018
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...
by ARSACS | Jul 27, 2018 | Research in 2018
The focus will be on Aim 1. The objective is to submit a paper that will elucidate the role of Sacsin and EndoB2 in dendritic spines that will include our BioID results. Aim 2. We will explore if a neuronal polarity defect in cytoskeletal protein trafficking might...
by ARSACS | Jul 27, 2018 | Research in 2018
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...
by ARSACS | Jul 27, 2018 | Research in 2018
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...
by ARSACS | Jul 27, 2018 | Research in 2018
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...
by ARSACS | Jul 27, 2018 | Research in 2018
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...
by ARSACS | Jul 27, 2018 | Research in 2018
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...
by ARSACS | Jul 27, 2018 | Research in 2018
The goal of this project is to develop therapeutic interventions that would ameliorate the degeneration of neurons in ARSACS. Specific Aims. 1. Test compounds that enhance mitochondrial motility in rat hippocampal neurons to determine if they also enhance motility in...
by ARSACS | Jul 27, 2018 | Research in 2018
This research consists of : 1. Establishing baseline measurements for our mitochondrial and cytoskeletal phenotypic readouts on the Perkin Elmer Opera Phenix High Content Screening platform. We will use tetramethylrhodamine methyl ester perchlorate (TMRM, a cationic...
by ARSACS | Jul 27, 2018 | Research in 2018
The current proposal proposes to capitalize on our discoveries and to move forward in two directions. First, pursue the protein/gene replacement approach until it produces a preclinical proof of concept that includes a translatable delivery method. Second, assess the...
