title: Hypomyelinating leukodystrophies: translational research progress and prospects.
abstract: Hypomyelinating leukodystrophies represent a genetically heterogeneous but clinically overlapping group of heritable disorders. Current management approaches in the care of the patient with a hypomyelinating leukodystrophy include use of serial magnetic resonance imaging (MRI) to establish and monitor hypomyelination, molecular diagnostics to determine a specific etiology, and equally importantly, careful attention to neurologic complications over time. Emerging research in oligodendrocyte biology and neuroradiology with bedside applications may result in the possibility of clinical trials in the near term, yet there are significant gaps in knowledge in disease classification, characterization, and outcome measures in this group of disorders. Here we review the biological background of myelination, the clinical and genetic variability in hypomyelinating leukodystrophies, and the insights that can be obtained from current MRI techniques. In addition, we discuss ongoing research approaches to define potential outcome markers for future clinical trials.
authors.affiliation: Department of Physics and Medical Technology, VU University Medical Center and Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
authors.forename: Petra J W
authors.initials: PJ
authors.lastname: Pouwels
authors.forename: Adeline
authors.initials: A
authors.lastname: Vanderver
authors.forename: Genevieve
authors.initials: G
authors.lastname: Bernard
authors.forename: Nicole I
authors.initials: NI
authors.lastname: Wolf
authors.forename: Steffi F
authors.initials: SF
authors.lastname: Dreha-Kulczewksi
authors.forename: Sean C L
authors.initials: SC
authors.lastname: Deoni
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertini
authors.forename: Alfried
authors.initials: A
authors.lastname: Kohlschütter
authors.forename: William
authors.initials: W
authors.lastname: Richardson
authors.forename: Charles
authors.initials: C
authors.lastname: Ffrench-Constant
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Köhler
authors.forename: David
authors.initials: D
authors.lastname: Rowitch
authors.forename: A James
authors.initials: AJ
authors.lastname: Barkovich
mesh_terms: D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000175:diagnosis* / Q000628:therapy; D006801:Humans; D008279:Magnetic Resonance Imaging; D057170:Translational Research, Biomedical