Monsanto Company

Oxford University Innovation Ltd

Actelion Pharmaceuticals Ltd

Other

The United States of America, As Represented by the Secretary, Department of Health and Human Services

Thomas Jefferson University

United Therapeutics Corporation

G.d. Searle & Company

The University of Oxford

Frances M Platt

Raymond A Dwek

Terry D Butters

Gabrielle R Neises

George W J Fleet

Terence D Butters

Timothy Michael Block

Gary S Jacob

Nicole Zitzmann

Anand Mehta

Donald H Picker

Michael Glen Orchard

Forbes Dennison Porter

Sandra Carrouee

David Durantel

Emyr Lloyd-Evans

Martin L Bryant

Baruch S Blumberg

Gunilla B Karlsson

Simon J Davis

Mylvaganam Jeyakumar

David Priestman

The present invention provides a compound which is an inhibitor of sphingolipid biosynthesis for use in the treatment of a disease which has a secondary Niemann-Pick type C disease like cellular phenotype.

Substrate reduction therapy

Pharmaceutically active piperidine derivatives

Long chain N-alkyl amino and imino compounds, oxa-substituted derivatives thereof, and pharmaceutical compositions including such compounds are described. The long chain N-alkyl group is a C-Calkyl group. The long chain N-alkyl compounds and oxa-substituted derivatives thereof can be used in the treatment of viral infections, in particular hepatitis B virus or hepatitis C virus, in a cell or an individual. For example, the long chain N-alkyl compounds or oxa-substituted derivatives thereof can be derived from piperidines, pyrrolidines, phenylamines, pyridines, pyrroles, or amino acids.

Long chain N-alkyl compounds and oxa-derivatives thereof

Long chain n-alkyl compounds and oxa-derivatives thereof

A method for treating a glycolipid storage-related disorder, comprising administering a therapeutically effective amount of an inhibitor of glycolipid synthesis in combination with an agent capable of increasing the rate of glycolipid degradation or in combination with bone marrow transplantation. Inhibitors of glycolipid synthesis include N-butyldeoxynojirimycin (NB-DNJ), N-butyldeoxygalactonojirimycin (NB-DGJ) or N-nonyldeoxynojirimycin (NN-DNJ). Glycolipid storage-related disorders include Gaucher disease, Sandhoff's disease, Fabry's disease, Tay-Sach's disease, Niemann-Pick C storage disease, GM1 gangliosidosis, genetic disorders in which neuronal glycolipid accumulation contributes to disease pathology.

Therapeutic compositions and methods of treating glycolipid storage related disorders

Methods for treating lipid storage diseases using compounds that inhibit glucosyltransferase enzymes are disclosed herein. The invention relates to the treatment of lipid storage disease with compounds that inhibit glucosyltransferase activity in the affected cells. It relates particularly to the use of 1,5-dideoxy-1,5-imino-D-glucitol and derivatives thereof.

Inhibition of glycolipid biosynthesis

A novel method is disclosed for the treatment of a patient affected with Gaucher's disease or other such glycolipid storage diseases. The method comprises administering to said patient a therapeutically effective amount of a long-chain N-alkyl derivative of deoxynojirimycin to alleviate or inhibit the glycolipid storage disease. The long-chain alkyl group has from nine to about 20 carbon atoms and preferably is nonyl or decyl.

Method for treatment of glycolipid storage diseases

Methods for inhibiting morphogenesis of host cell membrane-budding viruses and infections caused thereby using compounds that inhibit host cell glucosidase or glucosyltransferase enzymes. Methods for treating lipid storage diseases using compounds that inhibit glucosyl transferance enzymes.

Inhibition of membrane-associated viral replication

Novel N-alkyl derivatives of deoxygalactonojirimycin are provided in which said alkyl contains from 3-6 carbon atoms. These novel compounds are useful for selectively inhibiting glycolipid synthesis.

Deoxygalactonojirimycin derivatives

A method is disclosed for modifying the carbohydrate moiety on glycoproteins to facilitate the structural and functional analysis of said glycoproteins such as by NMR spectroscopic analysis and crystallography which comprises treating glycoprotein-secreting mammalian cells having low endomannosidase activity under cell culture maintenance conditions with a glucosidase I inhibitor, and after secretion and purification, subsequent treatment of the active glycoprotein with endoglycosidase H to thereby provide a glycoprotein with a single GlcNAc residue at each glycosylation sequon. The preferred mammalian cells are CHO cells and the preferred glucosidase I inhibitor is N-butyl deoxynojirimycin.

Method for carbohydrate engineering of glycoproteins

A method is disclosed for the treatment of Tay-Sachs disease comprising subjecting said cells to a glycolipid inhibitory effective amount of an N-alkyl derivative of 1,5-dideoxy-1,5-imino-D-glucitol in which said alkyl contains from 2-8 carbon atoms.

Method of treating Tay-Sachs disease

A method is disclosed for the in vivo treatment of patients having a lysosomal storage disease with a significant central nervous system (CNS) involvement. Said method comprises administration to said patient a small but storage-inhibitory effective amount of an N-alkyl derivative of a 1,5-iminosugar in which said alkyl group contains from about 2 to about 8 carbon atoms and said 1,5-iminosugar is 1,5-dideoxy-1,5-imino-D-glucitol, or 1,5-dideoxy-1,5-imino-D-galactitol, or an O-acylated pro-drug of said 1,5-iminosugar. In an illustrative example, CNS storage of GM2 ganglioside is inhibited in Tay-Sachs mice by administration of 1,5-(butylimino)-1,5-dideoxy-D-glucitol.

Method for treatment of CNS-involved lysosomal storage diseases

Growing community of inventors

Oxford, United Kingdom

Frances M Platt