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

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

Benoit Coulombe  1   2 , Alexandra Chapleau  3   4   5 , Julia Macintosh  3   4 , Thomas M Durcan  5 , Christian Poitras  1 , Yena A Moursli  1 , Denis Faubert  6 , Maxime Pinard  1 , Geneviève Bernard  3   4   7
Affiliations
Review

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

Benoit Coulombe et al. Biomolecules. .

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.

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Conflict of interest statement

Dr. Bernard is/was a consultant for Calico (2023–present), Orchard Therapeutics (2023-present), Passage Bio Inc (2020–2022), and Ionis (2019). She is/was a site investigator for the Alexander’s disease trial of Ionis (2021–present), the metachromatic leukodystrophy trial of Shire/Takeda (2020–2021) and Krabbe (2021–2023), the GM1 gene therapy trials of Passage Bio (2021–present), the GM1 natural history study from the University of Pennsylvania sponsored by Passage Bio (2021–present), and the adrenoleukodystrophy/hematopoietic stem cell transplantation natural history study of Bluebird Bio (2019), as well as a site sub-investigator for the MPS II gene therapy trial of Regenxbio (2021–present) and the MPS II clinical trial of Denali (2022–present). She has received an unrestricted educational grant from Takeda (2021–2022).

Figures

Figure 1
Figure 1
Scheme for cell-based interception and precision medicine applied to leukodystrophies.
Figure 2
Figure 2
Schematic representation of the 17-subunit Pol III complex. Leukodystrophy-causative mutations were found in the subunits marked in dark grey.
See this image and copyright information in PMC

References

    1. LifeTime. Biomedical Research Initiative. [(accessed on 1 May 2024)]. Available online: https://lifetime-initiative.eu.
    1. Rajewsky N., Almouzni G., Gorski S.A., Aerts S., Amit I., Bertero M.G., Bock C., Bredenoord A.L., Cavalli G., Chiocca S., et al. LifeTime and improving European healthcare through cell-based interceptive medicine. Nature. 2020;587:377–386. doi: 10.1038/s41586-020-2715-9. - DOI - PMC - PubMed
    1. 37TrilllionCells. [(accessed on 1 May 2024)]. Available online: https://37TrillionCells.com.
    1. Thiffault I., Wolf N.I., Forget D., Guerrero K., Tran L.T., Choquet K., Lavallee-Adam M., Poitras C., Brais B., Yoon G., et al. Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III. Nat. Commun. 2015;6:7623. doi: 10.1038/ncomms8623. - DOI - PMC - PubMed
    1. Choquet K., Forget D., Meloche E., Dicaire M.J., Bernard G., Vanderver A., Schiffmann R., Fabian M.R., Teichmann M., Coulombe B., et al. Leukodystrophy-associated POLR3A mutations down-regulate the RNA polymerase III transcript and important regulatory RNA BC200. J. Biol. Chem. 2019;294:7445–7459. doi: 10.1074/jbc.RA118.006271. - DOI - PMC - PubMed

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