Krabbe disease: One Hundred years from the bedside to the bench to the bedside.

J Neurosci Res 2016 11;94(11):982-9

Department of Neurology, Sidney Kimmel College of Medicine at Thomas Jefferson University, Philadelphia, Pennsylvania.

This Review summarizes the progress in understanding the pathogenesis and treatment of Krabbe disease from the description of five patients in by Knud Krabbe until 2016. To determine the cause of this genetic disease, pathological and chemical analyses of tissues from the nervous systems of patients were performed. It was determined that these patients had a pathological feature known as globoid cell in the brain and that this consisted partially of galactosylceramide, a major sphingolipid component of myelin. The finding that these patients had a deficiency of galactocerebrosidase (GALC) activity opened the way to relatively simple diagnostic testing with easily obtainable tissue samples, studies leading to the purification of GALC, and cloning of the GALC cDNA and gene. The availability of the gene sequence led to the identification of mutations in patients and to the current studies involving the use of viral vectors containing the GALC cDNA to treat experimentally naturally occurring animal models, such as twitcher mice. Currently, treatment of presymptomatic human patients is limited to hematopoietic stem cell transplantation (HSCT). With recent studies showing successful treatment of animal models with a combination of HSCT and viral gene therapy, it is hoped that more effective treatments will soon be available for human patients. For this Review, it is not possible to reference all of the articles contributing to our current state of knowledge about this disease; however, we have chosen those that have influenced our studies by suggesting research paths to pursue. © 2016 Wiley Periodicals, Inc.

Download full-text PDF

Source
http://dx.doi.org/10.1002/jnr.23743DOI Listing
November 2016
2 Reads

Publication Analysis

Top Keywords

galc cdna
8
human patients
8
animal models
8
krabbe disease
8
patients
7
current studies
4
studies involving
4
involving viral
4
patients current
4
mutations patients
4
led identification
4
identification mutations
4
viral vectors
4
cdna treat
4
models twitcher
4
twitcher mice
4
mice currently
4
occurring animal
4
naturally occurring
4
sequence led
4

Similar Publications