title: Treatment for Krabbe's disease: Finding the combination.
abstract: Globoid cell leukodystrophy (GLD) is an autosomal recessive neurodegenerative disorder caused by a deficiency of the lysosomal enzyme galactocerebrosidase (GALC). GALC is responsible for catabolism of certain glycolipids, including the toxic compound galactosylsphingosine (psychosine). Histological signs of disease include the widespread loss of myelin in the central and peripheral nervous systems, profound neruroinflammation, and axonal degeneration. Patients suffering from GLD also display neurological deterioration. Many different individual therapies have been investigated in the murine model of the GLD, the Twitcher mouse, with minimal success. The current standard of care for GLD patients, hematopoietic stem cell transplantation, serves only to delay disease progression and is not an effective cure. However, combination therapies that target different pathogenic mechanisms/pathways have been more effective at reducing histological signs of disease, delaying disease onset, prolonging life span, and improving behavioral/cognitive functions in rodent models of Krabbe's disease. In some cases, dramatic synergy between the various therapies has been observed. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri.|Department of Genetics, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Christina R
authors.initials: CR
authors.lastname: Mikulka
authors.affiliation: Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri. msands@dom.wustl.edu.|Department of Genetics, Washington University School of Medicine, St. Louis, Missouri. msands@dom.wustl.edu.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Sands
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D003131:Combined Modality Therapy / Q000379:methods*; D003523:Cycloserine / Q000627:therapeutic use; D004195:Disease Models, Animal; D056947:Enzyme Replacement Therapy; D005698:Galactosylceramidase / Q000172:deficiency; D015316:Genetic Therapy; D006801:Humans; D007965:Leukodystrophy, Globoid Cell / Q000235:genetics / Q000378:metabolism / Q000628:therapy*
chemical_list: D000893:Anti-Inflammatory Agents; D003523:Cycloserine; D005698:Galactosylceramidase
keywords: Krabbe's disease; bone marrow transplant; galactocerebrosidase; gene therapy; lysosomal storage disease