Developing a National Network for Leukodystrophy Research and Care in Canada: The CARELeuko Initiative

Alexandra Chapleau^{1

2

3

4}, Adam Le¹, Justin Simo^{2

3}, Sunita Venkateswaran⁵, Thierry Lacaze-Masmonteil⁶, Valerio E C Piscopo^{2

3}, Samuel Gauthier^{1

7}, Felipe Villa Tobón^{1

2}, Sabrina Shameen Alam¹, Laura Lentini¹, Bernard Brais^{2

7}, Carl Ernst^{2

7

8}, John J Mitchell^{1

9

7

10}, Donald C Vinh^{11

12

13

14

15

7}, Yang Zhou², Timothy E Kennedy², Naomi Goloff^{16

10}, Badawy Riham¹⁷, Ron Chapleau^{18

4}, Ben Smith¹⁹, Valerie Greger¹⁹, Josée Della Rocca²⁰, Lynda-Marie Louis²¹, Ashley Dike²², Lindey L McIntyre²³, David F McIntyre²³, Jérome Tardif²⁴, Émilie Lapointe²⁵, Jennifer Barnett²⁶, Valérie Loignon²⁶, Ghalib Bardai²⁶, Sophie Contant²⁶, Thomas M Durcan^{2

3}, Roberta La Piana^{2

27}, Geneviève Bernard^{1

2

28

7

10}; as RareKids-CAN, RARE.Qc, CARELeuko

Affiliations

¹ Child Health and Human Development Program, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
² Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
³ The Neuro's Early Drug Discovery Unit (EDDU), McGill University, Montreal, Quebec, Canada.
⁴ Alliance MLC, Middletown, DE.
⁵ Division of Neurology, Children's Hospital, London Health Sciences Center, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
⁶ Maternal Infant Child and Youth Research Network (MICYRN), Vancouver, British Columbia, Canada.
⁷ Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
⁸ Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
⁹ Division of Pediatric Endocrinology, McGill University Health Centre, Montreal, Quebec, Canada.
¹⁰ Department of Pediatrics, McGill University, Montreal, Quebec, Canada.
¹¹ Department of Medicine, Division Experimental Medicine, McGill University, Quebec, Canada.
¹² Department of Medical Microbiology, McGill University, Quebec, Canada.
¹³ Department of Microbiology and Immunology, McGill University, Quebec, Canada.
¹⁴ Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
¹⁵ Department of Medicine, Division of Infectious Diseases, McGill University Health Centre, Montreal, Quebec, Canada.
¹⁶ Division of Pediatric Palliative Medicine, McGill University Health Centre, Montreal, Quebec, Canada.
¹⁷ ALD Hope, Oakville, Ontario, Canada.
¹⁸ The United Leukodystrophy Foundation, Dekalb, IL.
¹⁹ The Yaya Foundation for 4H Leukodystrophy, St. Louis Park, MN.
²⁰ The Montreal Children's Hospital Foundation, Montreal, Quebec, Canada.
²¹ Fondation le tout pour Loo, Blainville, Quebec, Canada.
²² LCC Foundation, Lake Saint Louis, MO.
²³ Bethanys Hope Foundation, London, Ontario, Canada.
²⁴ Fondation les amis d'Elliot, Victoriaville, Quebec, Canada.
²⁵ Leuco-Action, Cantley, Quebec, Canada.
²⁶ None.
²⁷ Department of Diagnostic Radiology, McGill University, Montreal, Quebec, Canada; and.
²⁸ Division of Medical Genetics, Department of Specialized Medicine, McGill University Health Centre, Montreal, Quebec, Canada.

PMID: 41143125
PMCID: PMC12552058
DOI: 10.1212/NXG.0000000000200313

Review

Developing a National Network for Leukodystrophy Research and Care in Canada: The CARELeuko Initiative

Alexandra Chapleau et al. Neurol Genet. 2025.

. 2025 Oct 23;11(6):e200313.

doi: 10.1212/NXG.0000000000200313. eCollection 2025 Dec.

Authors

Affiliations

¹ Child Health and Human Development Program, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
² Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
³ The Neuro's Early Drug Discovery Unit (EDDU), McGill University, Montreal, Quebec, Canada.
⁴ Alliance MLC, Middletown, DE.
⁵ Division of Neurology, Children's Hospital, London Health Sciences Center, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
⁶ Maternal Infant Child and Youth Research Network (MICYRN), Vancouver, British Columbia, Canada.
⁷ Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
⁸ Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
⁹ Division of Pediatric Endocrinology, McGill University Health Centre, Montreal, Quebec, Canada.
¹⁰ Department of Pediatrics, McGill University, Montreal, Quebec, Canada.
¹¹ Department of Medicine, Division Experimental Medicine, McGill University, Quebec, Canada.
¹² Department of Medical Microbiology, McGill University, Quebec, Canada.
¹³ Department of Microbiology and Immunology, McGill University, Quebec, Canada.
¹⁴ Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
¹⁵ Department of Medicine, Division of Infectious Diseases, McGill University Health Centre, Montreal, Quebec, Canada.
¹⁶ Division of Pediatric Palliative Medicine, McGill University Health Centre, Montreal, Quebec, Canada.
¹⁷ ALD Hope, Oakville, Ontario, Canada.
¹⁸ The United Leukodystrophy Foundation, Dekalb, IL.
¹⁹ The Yaya Foundation for 4H Leukodystrophy, St. Louis Park, MN.
²⁰ The Montreal Children's Hospital Foundation, Montreal, Quebec, Canada.
²¹ Fondation le tout pour Loo, Blainville, Quebec, Canada.
²² LCC Foundation, Lake Saint Louis, MO.
²³ Bethanys Hope Foundation, London, Ontario, Canada.
²⁴ Fondation les amis d'Elliot, Victoriaville, Quebec, Canada.
²⁵ Leuco-Action, Cantley, Quebec, Canada.
²⁶ None.
²⁷ Department of Diagnostic Radiology, McGill University, Montreal, Quebec, Canada; and.
²⁸ Division of Medical Genetics, Department of Specialized Medicine, McGill University Health Centre, Montreal, Quebec, Canada.

PMID: 41143125
PMCID: PMC12552058
DOI: 10.1212/NXG.0000000000200313

Abstract

Leukodystrophies (LDs) are a group of rare, genetic disorders unified by their hallmark involvement of the cerebral white matter. They are typically characterized as progressive disorders, resulting in severe neurologic decline and premature death within months to years after onset. Managing LDs therefore requires lifelong, multidisciplinary care, a challenge compounded by their rarity and phenotypic heterogeneity, for which detailed clinical and scientific information is sometimes lacking. Research networks have proven useful in the rare disease community to unite efforts, increase awareness, and accelerate progress toward understanding and treating these often understudied conditions. Therefore, we established the Canadian Association for Research Excellence in Leukodystrophy (CARELeuko), a national network dedicated to improving LD care, research, and treatment within Canada. To better understand and address the most pressing needs for LDs in Canada, we engaged a diverse group of stakeholders including researchers, clinicians, and patient advocates to highlight and prioritize gaps in LD care and research. In this review, we discuss the key gaps identified in the Canadian LD landscape and outline strategies to address these challenges. This effort will inform the development of targeted initiatives aimed at improving outcomes for Canadian families affected by these debilitating disorders.

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Conflict of interest statement

A. Chapleau, A. Le, J. Simo, S. Venkateswaran, T. Lacaze-Masmonteuil, V.E.C. Piscopo, and S. Gauthier report no disclosures on the manuscript; F.V. Tobón is a subinvestigator for the IONIS ION373 Trial for Alexander's disease; S.S. Alam, L. Lentini, B. Brais, and C. Ernst report no disclosures on the manuscript; J. Mitchell is a chair of the scientific advisory board for the Canadian mucopolysaccharidosis (MPS) association of Canada, a site investigator for the MPS II gene therapy trial of Regenxbio (2021–present), the MPS II clinical trial of Denali (2022–present), the Biomarin Morquio A registry (2015–present), the Sanofi MPS I registry (2005–present), and has served as a subinvestigator on Krabbe (2021–2023) and GM1 gene therapy trials of Passage Bio (2021–2024); D.C. Vinh has served on advisory boards for Astra Zeneca, CSL Behring, Novartis Canada, Moderna, and Takeda, he has received speaker honoraria from CSL Behring and Merck Canada, he has a patent application pending (Electronic Filing System ID: 40101099) unrelated to this work; Y. Zhou, T.E. Kennedy, N. Goloff, B. Riham, R. Chapleau, B. Smith, V. Greger, J.D. Rocca, L.M. Louis, A. Dike, L.L. McIntyre, D. McIntyre, J. Tardif, E. Lapointe, J. Barnett, V. Loignon, G. Bardai, S. Contant, and T.M. Durcan report no disclosures on the manuscript; R. La Piana serves on the Medical and Scientific Advisory Committee of Sisters' Hope Foundation and is on the editorial boards of Annals of Neurology and is Review Editor for Frontiers in Genetics. G. Bernard is/was a consultant for Calico (2023–present), Orchard Therapeutics (2023), Passage Bio Inc (2020–2022), and Ionis (2019), she is/was a site investigator for the Vanishing White Matter trial of Calico/Abbvie (2025-present), Alexander's disease trial of Ionis (2021–present), Metachromatic leukodystrophy of Shire/Takeda (2020–2021), Krabbe (2021–2023), and GM1 gene therapy trials of Passage Bio (2021–2024), GM1 natural history study from the University of Pennsylvania sponsored by Passage Bio (2021–present), and Adrenoleukodystrophy/HSCT natural history study of Bluebird Bio (2019), a site subinvestigator 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). She serves on the Scientific Advisory Board of the Pelizaeus-Merzbacher Foundation, the Yaya Foundation Scientific and Clinical Advisory Council and the Medical and Scientific Advisory Board of the United Leukodystrophy Foundation. She is a member of the Vanishing White Matter Consortium, H-ABC Clinical Advisory Board, MLC Clinical Expert Consortium, and the Chair of the POLR3-related (4H) Leukodystrophy Consortium. She is on the editorial boards of Neurology® Genetics, Frontiers in Neurology—Neurogenetics, and Journal of Medical Genetics. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/NG.

Figures

**Figure. Geographical Representation of Specialized LD Centers or Networks Located Mainly in North America and Europe**
Canadian centers where LD specialists' practice is highlighted in red. LD = leukodystrophy.

See this image and copyright information in PMC

References

1. One in 12 Canadians Has a Rare Disorder. Approximately, 3 Million Canadians and Their Families Face a Debilitating Disease that Severely Impacts Their Lives. Canadian Organization for Rare Disorders; raredisorders.ca/about-cord/ (2021).
1. Investments to Support Access to Drugs for Rare Diseases. Government of Canada, Health Canada; canada.ca/en/health-canada/news/2023/03/investments-to-support-access-to... (2023).
1. Boycott KM, Hartley T, Kernohan KD, et al. Care4Rare Canada: outcomes from a decade of network science for rare disease gene discovery. Am J Hum Genet. 2022;109(11):1947-1959. doi: 10.1016/j.ajhg.2022.10.002 - DOI - PMC - PubMed
1. Boycott KM, Campeau PM, Howley HE, et al. The Canadian rare diseases models and mechanisms (RDMM) network: connecting understudied genes to model organisms. Am J Hum Genet. 2020;106(2):143-152. doi: 10.1016/j.ajhg.2020.01.009 - DOI - PMC - PubMed
1. RareKids-CAN: Pediatric Rare Disease Clinical Trials and Treatment Network. RareKids-CAN; rarekidscan.com (n.d., 2024).

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Developing a National Network for Leukodystrophy Research and Care in Canada: The CARELeuko Initiative

Affiliations

Developing a National Network for Leukodystrophy Research and Care in Canada: The CARELeuko Initiative

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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