Towards a Treatment for Leukodystrophy Using Cell-Based Interception and Precision Medicine

Benoit Coulombe; Alexandra Chapleau; Julia Macintosh; Thomas M Durcan; Christian Poitras; Yena A Moursli; Denis Faubert; Maxime Pinard; Geneviève Bernard

doi:10.3390/biom14070857

Towards a Treatment for Leukodystrophy Using Cell-Based Interception and Precision Medicine

Biomolecules. 2024 Jul 17;14(7):857. doi: 10.3390/biom14070857.

Authors

Benoit Coulombe^{1

2}, Alexandra Chapleau^{3

4

5}, Julia Macintosh^{3

4}, Thomas M Durcan⁵, Christian Poitras¹, Yena A Moursli¹, Denis Faubert⁶, Maxime Pinard¹, Geneviève Bernard^{3

4

7}

Affiliations

¹ Translational Proteomics Laboratory, Institut de Recherches Cliniques de Montréal, Montréal, QC H2W 1R7, Canada.
² Department of Biochemistry and Molecular Medicine, Université de Montréal, Montréal, QC H3T 1A8, Canada.
³ Department of Neurology and Neurosurgery, Pediatrics and Human Genetics, McGill University, Montréal, QC H9X 3V9, Canada.
⁴ Child Health and Human Development Program, Research Institute of the McGill University Health Centre, Montréal, QC H4A 3J1, Canada.
⁵ The Neuro's Early Drug Discovery Unit (EDDU), McGill University, Montréal, QC H9X 3V9, Canada.
⁶ Mass Spectrometry and Proteomics Platform, Institut de Recherches Cliniques de Montréal, Montréal, QC H2W 1R7, Canada.
⁷ Department Specialized Medicine, Division of Medical Genetics, McGill University Health Centre, Montréal, QC H4A 3J1, Canada.

Abstract

Cell-based interception and precision medicine is a novel approach aimed at improving healthcare through the early detection and treatment of diseased cells. Here, we describe our recent progress towards developing cell-based interception and precision medicine to detect, understand, and advance the development of novel therapeutic approaches through a single-cell omics and drug screening platform, as part of a multi-laboratory collaborative effort, for a group of neurodegenerative disorders named leukodystrophies. Our strategy aims at the identification of diseased cells as early as possible to intercept progression of the disease prior to severe clinical impairment and irreversible tissue damage.

Keywords: POLR3-related leukodystrophy (POLR3-HLD); SCoPE2-MS; cell-based interception and precision medicine; induced pluripotent stem cells; leukodystrophy; proteomics; single-cell technologies.

Publication types

Review

MeSH terms

Animals
Humans
Precision Medicine* / methods
Single-Cell Analysis / methods

Grants and funding

The cell-based interception and precision medicine developed by our group has so far been supported by the Ministère de l’Économie, de l’Innovation et de l’Énergie (MEIE) of the Government of Québec, the IRCM foundation, and the private investor WinnerMax Capital Inc., demonstrating an interest in this project. Analysis of leukodystrophy mechanisms is supported by the Canadian Institutes of Health Research (CIHR) (BC and GB), the Fondation leucodystrophies (BC), the Yaya Foundation for 4H Leukodystrophy (GB), the Fondation Les Amis d’Élliot (GB), the Fondation Le Tout pour Loo (GB), the Fondation du Grand Défi Pierre Lavoie (GB), the Research Institute of the McGill University Health Centre (GB), Leuco-Action, and the Montreal Children’s Hospital Foundation (GB). Geneviève Bernard has received the Clinical Research Scholar Junior 1 Award from the Fonds de Recherche du Québec-Santé (FRQS) (2012–2016), the New Investigator Salary Award from the Canadian Institutes of Health Research (2017–2022), and the Clinical Research Scholar Senior award from the FRQS (2022–2025). Thomas M Durcan received funding through the McGill Healthy Brains for Healthy Lives (HBHL) initiative, the CQDM Quantum Leaps program with support from Brain Canada, the Alain and Sandra Bouchard Foundation, the Sebastien and Ghislaine Van Berkom Foundation, Médicament Québec, the Chamandy Foundation, and the Mowafaghian Foundation. TMD is supported by a project grant from CIHR (PJT-169095). BC is supported by the Bell-Bombardier Chair of Excellence at the IRCM.