Lachmann, Robin H., te Vruchte, Danielle, Lloyd-Evans, Emyr  ORCID: https://orcid.org/0000-0002-3626-1611, Reinkensmeier, Gabriele, Sillence, Daniel J., Fernandez-Guillen, Luisa, Dwek, Raymond A., Butters, Terry D., Cox, Timothy M. and Platt, Frances M.
2004.
Treatment with miglustat reverses the lipid-trafficking defect in Niemann–Pick disease type C.
Neurobiology of Disease
16
(3)
, pp. 654-658.
10.1016/j.nbd.2004.05.002
|
Abstract
Niemann–Pick disease type C (NP-C) is a hereditary neurovisceral lipid storage disorder. Although traditionally considered a primary cholesterol storage disorder, a variety of glycolipids accumulate in NP-C cells, which resemble those from glycosphingolipidosis patients. Substrate reduction therapy (SRT) with miglustat, an inhibitor of glycosphingolipid biosynthesis, is a novel therapy for the glycosphingolipidoses. We report the use of SRT in a patient with NP-C. We show that depletion of glycosphingolipids by miglustat treatment reduces pathological lipid storage, improves endosomal uptake and normalises lipid trafficking in peripheral blood B lymphocytes. The demonstration that treatment with miglustat, which has no direct effect on cholesterol metabolism, corrects the abnormal lipid trafficking seen in B lymphocytes in NP-C indicates that glycosphingolipid accumulation is the primary pathogenetic event in NP-C. These observations support the use of SRT in patients with this devastating neurodegenerative disease.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Biosciences |
| Publisher: | Elsevier |
| ISSN: | 0969-9961 |
| Last Modified: | 27 Oct 2022 08:48 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/63431 |
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