Biomedical subjects

Robin H Lachmann

Publications and source records attributed to Robin H Lachmann.

4 recordsLinked to original sources

PubMed2006

Miglustat: substrate reduction therapy for glycosphingolipid lysosomal storage disorders.

Substrate reduction therapy offers a novel approach to the treatment of lysosomal storage disorders. By reducing the rate of macromolecule synthesis to a level where the residual degradative activity in the cell is sufficient to prevent substrate accumulation, it should be possible to reverse storage and storage-related pathologies. Miglustat is an N-alkylated imino sugar that acts against a number of enzymes involved in processing glycoconjugates, including the ceramide-specific glucosyltransferase, which catalyzes the initial committed step in glycosphingolipid synthesis. Miglustat could therefore be used for substrate reduction therapy in glycosphingolipid lysosomal storage disorders. This article addresses both the preclinical and clinical development of miglustat for treatment of type 1 Gaucher's disease, as well as related neuronopathic glycosphingolipidoses.

1-Deoxynojirimycin↗

PubMed2004

Treatment with miglustat reverses the lipid-trafficking defect in Niemann-Pick disease type C.

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.

Adult↗

PubMed2004

alpha-glucosidase (CHO) (Genzyme).

Genzyme General is developing recombinant human alpha-glucosidase, produced in mammalian cell culture, as a potential treatment for Pompe disease. By July 2004, enrollment was completed in two clinical trials and an observational study in adults. Genzyme was planning to file for regulatory approval in Europe during 2004, followed by filings in the US and Japan in mid-2005.

Animals↗

PubMed2003

Miglustat. Oxford GlycoSciences/Actelion.

Oxford GlycoSciences and Actelion have developed and launched miglustat (OGT-918; Vevesca; Zavesca) for the treatment of type 1 Gaucher disease. Miglustat is an orally administered small-molecule glucosylceramide glucosyltransferase inhibitor licensed from Searle, and it is also in development for the treatment of other glycolipid storage disorders such as Tay-Sachs, Fabry and Niemann-Pick type C diseases. In November 2002, miglustat received EU approval for the treatment of Gaucher disease and was launched in the UK in March 2003 by Actelion. At this time, additional EU launches were expected over the next few months.

Animals↗