Update on leukodystrophies and developing trials

• Published in: Journal of neurology Vol. 271; no. 1; pp. 593 - 605
• Main Authors: Ceravolo, Giorgia, Zhelcheska, Kristina, Squadrito, Violetta, Pellerin, David, Gitto, Eloisa, Hartley, Louise, Houlden, Henry
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-01-2024; Springer Nature B.V
• Subjects: Ataxia; Central nervous system; Clinical trials; Cysts; Demyelinating Diseases; Diagnosis; Disease; Gene therapy; Genetic disorders; Genetic screening; Genetic testing; Hereditary Central Nervous System Demyelinating Diseases - diagnosis; Hereditary Central Nervous System Demyelinating Diseases - genetics; Hereditary Central Nervous System Demyelinating Diseases - therapy; Humans; Leukodystrophy; Lysosomal Storage Diseases; Magnetic Resonance Imaging; Medical imaging; Medical screening; Medicine; Medicine & Public Health; Metabolism; Nervous system; Neuroimaging; Neurological Update; Neurology; Neuroradiology; Neurosciences; Pathophysiology; Spasticity; Spinal cord; Substantia alba; White Matter; Leukodystrophy; Trials; Genetic testing
• ISSN: 0340-5354; 1432-1459
• DOI: 10.1007/s00415-023-11996-5

Leukodystrophies are a heterogeneous group of rare genetic disorders primarily affecting the white matter of the central nervous system. These conditions can present a diagnostic challenge, requiring a comprehensive approach that combines clinical evaluation, neuroimaging, metabolic testing, and genetic testing. While MRI is the main tool for diagnosis, advances in molecular diagnostics, particularly whole-exome sequencing, have significantly improved the diagnostic yield. Timely and accurate diagnosis is crucial to guide symptomatic treatment and assess eligibility to participate in clinical trials. Despite no specific cure being available for most leukodystrophies, gene therapy is emerging as a potential treatment avenue, rapidly advancing the therapeutic prospects in leukodystrophies. This review will explore diagnostic and therapeutic strategies for leukodystrophies, with particular emphasis on new trials.