Disease specific therapies in leukodystrophies and leukoencephalopathies

Guy Helman; Keith Van Haren; Joshua L Bonkowsky; Genevieve Bernard; Amy Pizzino; Nancy Braverman; Dean Suhr; Marc C Patterson; S Ali Fatemi; Jeff Leonard; Marjo S van der Knaap; Stephen A Back; Stephen Damiani; Steven A Goldman; Asako Takanohashi; Magdalena Petryniak; David Rowitch; Albee Messing; Lawrence Wrabetz; Raphael Schiffmann; Florian Eichler; Maria L Escolar; Adeline Vanderver; GLIA Consortium

doi:10.1016/j.ymgme.2015.01.014

Disease specific therapies in leukodystrophies and leukoencephalopathies

Mol Genet Metab. 2015 Apr;114(4):527-36. doi: 10.1016/j.ymgme.2015.01.014. Epub 2015 Feb 7.

Authors

Guy Helman¹, Keith Van Haren², Joshua L Bonkowsky³, Genevieve Bernard⁴, Amy Pizzino², Nancy Braverman⁵, Dean Suhr⁶, Marc C Patterson⁷, S Ali Fatemi⁸, Jeff Leonard⁹, Marjo S van der Knaap¹⁰, Stephen A Back¹¹, Stephen Damiani¹², Steven A Goldman¹³, Asako Takanohashi¹⁴, Magdalena Petryniak¹⁵, David Rowitch¹⁶, Albee Messing¹⁷, Lawrence Wrabetz¹⁸, Raphael Schiffmann¹⁹, Florian Eichler²⁰, Maria L Escolar²¹, Adeline Vanderver²²; GLIA Consortium

Affiliations

¹ Department of Neurology, Children's National Health System, Washington, DC, USA.
² Department of Neurology, Lucile Packard Children's Hospital and Stanford University School of Medicine, Stanford, CA, USA.
³ Department of Pediatrics and Neurology, University of Utah School of Medicine, Salt Lake City, UT, USA.
⁴ Department of Pediatrics, Montreal Children's Hospital/McGill University Health Center, Montreal, Canada; Department of Neurology and Neurosurgery, Montreal Children's Hospital/McGill University Health Center, Montreal, Canada.
⁵ Department of Human Genetics and Pediatrics, McGill University and the Montreal Children's Hospital Research Institute, Montreal, Canada.
⁶ MLD Foundation, USA.
⁷ Department of Neurology, Mayo Clinic, Rochester, MN, USA; Department of Pediatrics and Medical Genetics, Mayo Clinic, Rochester, MN, USA.
⁸ The Moser Center for Leukodystrophies and Neurogenetics Service, The Kennedy Krieger Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA.
⁹ The PMD Foundation, USA.
¹⁰ Department of Child Neurology, VU University Medical Center, and Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
¹¹ Department of Pediatrics and Neurology, Oregon Health and Science University, Portland, OR, USA.
¹² Mission Massimo Foundation Inc., Melbourne, VIC, Australia; Mission Massimo Foundation Inc., Los Angeles, CA, USA.
¹³ Center for Translational Neuromedicine and the Department of Neurology of the University of Rochester Medical Center, Rochester, NY, USA.
¹⁴ Center for Genetic Medicine Research, Children's National Health System, Washington, DC USA.
¹⁵ Department of Pediatrics, Papé Family Pediatric Research Institute, Oregon Health and Science University, Portland, OR, USA.
¹⁶ Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
¹⁷ Waisman Center and Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, WI, USA.
¹⁸ Department of Neurology, Hunter James Kelly Research Institute-HJRKI, University of Buffalo School of Medicine and Biomedical Sciences, Buffalo, NY, USA; Department of Biochemistry, Hunter James Kelly Research Institute-HJRKI, University of Buffalo School of Medicine and Biomedical Sciences, Buffalo, NY, USA.
¹⁹ Institute of Metabolic Disease, Baylor Research Institute, Dallas, TX, USA.
²⁰ Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
²¹ Department of Pediatrics, University of Pittsburgh, One Children's Hospital Drive, Pittsburgh, PA, USA.
²² Department of Neurology, Children's National Health System, Washington, DC, USA; Center for Genetic Medicine Research, Children's National Health System, Washington, DC USA; Department of Integrated Systems Biology, George Washington University School of Medicine, Washington, DC, USA. Electronic address: avanderv@childrensnational.org.

Abstract

Leukodystrophies are a heterogeneous, often progressive group of disorders manifesting a wide range of symptoms and complications. Most of these disorders have historically had no etiologic or disease specific therapeutic approaches. Recently, a greater understanding of the pathologic mechanisms associated with leukodystrophies has allowed clinicians and researchers to prioritize treatment strategies and advance research in therapies for specific disorders, some of which are on the verge of pilot or Phase I/II clinical trials. This shifts the care of leukodystrophy patients from the management of the complex array of symptoms and sequelae alone to targeted therapeutics. The unmet needs of leukodystrophy patients still remain an overwhelming burden. While the overwhelming consensus is that these disorders collectively are symptomatically treatable, leukodystrophy patients are in need of advanced therapies and if possible, a cure.

Keywords: Care; Consensus; Leukodystrophy; Outcomes; Prevention; Therapy.

Publication types

Consensus Development Conference
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Brain Diseases / prevention & control
Brain Diseases / therapy
Demyelinating Diseases / prevention & control
Demyelinating Diseases / therapy*
Hereditary Central Nervous System Demyelinating Diseases / prevention & control
Hereditary Central Nervous System Demyelinating Diseases / therapy*
Humans
Leukodystrophy, Metachromatic / prevention & control
Leukodystrophy, Metachromatic / therapy*
Leukoencephalopathies / prevention & control
Leukoencephalopathies / therapy*

Abstract

Publication types

MeSH terms

Grants and funding