Oxford University Innovation Limited

United Therapeutics Corporation

Other

Thomas Jefferson University

Emergent Virology LLC

Shox Science Limited

Unither Virology, LLC

National Institute for Bioprocessing Research and Training Limited (nibrt)

The Chancellor, Masters and Scholars of the University of Oxford

University of Oxford

Nicole Zitzmann

Raymond A Dwek

Terry D Butters

Urban Ramstedt

Brennan Klose

Bevin Gangadharan

Timothy Michael Block

Frances M Platt

Anand Mehta

Gary S Jacob

Donald H Picker

George W J Fleet

Abhinav Kumar

Pauline Rudd

Catherine M Radcliffe

Louise Royle

Stephanie Pollock

David Durantel

Sandra Carrouee

Jeremy Francis Lars Cobbold

Mark Thursz

Robert M Moriarty

Baruch S Blumberg

John M Robertson

J L Kiappes

Peter Laing

Livia Zdrentu

Norica Nichita

Gabriela Negroiu

Anca Hirtopeanu

Umi Marshida Abd Hamid

Rafael De Llorens

Rosa Peracaula

Raymond Allen Dwek Frs

Wanda Buzgariu

The invention relates to methods of diagnosing, prognosing, or monitoring or staging the progression of non-alcoholic fatty liver disease (NAFLD) using biomarkers. The invention also relates to a method of scoring to determine the severity of NAFLD, and a method of treating NAFLD.

Clinical diagnosis of non-alcoholic fatty liver disease using a panel of human blood protein biomarkers

Provided are methods of treating or preventing viral infections caused by or associated with a Dengue virus using iminosugars.

Iminosugars and methods of treating viral diseases

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

The inventors have proposed a novel panel of human serum protein biomarkers for diagnosing hepatic fibrosis and cirrhosis. Presently there is no reliable non-invasive way of assessing liver fibrosis. A 2D-PAGE based proteomics study was used to identify potential fibrosis biomarkers. Serum from patients with varying degrees of hepatic scarring induced by infection with the hepatitis C virus (HCV) was analyzed. Several proteins associated with liver scarring and/or viral infection were identified. These proteins include the inter-&#x3b1;-trypsin inhibitor heavy chain H4 fragments, complement factor H-related protein 1, CD5L, Apo L1, and &#x3b2;2GPI. Increased and decreased thiolester cleavage of a2M and Complement C3, respectively, was also detected. The concentrations of these novel biomarkers can be determined using an immunoassay where the concentrations would reflect the extent of fibrosis. A fibrosis scoring scale for each of the novel biomarkers is proposed. The additive result from the scores of all the novel biomarkers would give a more reliable indication of the degree of fibrosis rather than examining individual biomarkers.

Clinical diagnosis of hepatic fibrosis using a novel panel of human serum protein biomarkers

A proliferation of cells can be reduced by contacting the cells with a compound having formula (I) where R and R' are each alkyl groups, R&#x2033; is hydrogen or an alkyl group and X, Xand Xare each independently selected from the group consisting of hydrogen, benzyl, t-butyldimethylsiloxy radical and triphenylmethyl. Accordingly, compounds of formula (I) can be used for treatment of tumors including melanoma. Also a secretion of a matrix metalloproteinase (MMP) enzyme by cells can be reduced by contacting the cells with the compound having formula (I). Accordingly, compounds of formula (I) can be used for treatment physiological conditions associated with an elevated MMP level, such as tumors.

Iminosugar treatment of tumors

Iminosugar compounds are described that have inbuilt delivery features by virtue of covalent incorporation of a tocopherol moiety, or alternative moieties that are analogs of tocopherol or select analogs of cholesterol, or its antagonist 'Ezitimibe'; and are likely to have broad spectrum antiviral activity. The compounds differ from previous iminosugar compounds, even lipophillic ones, being more hydrophobic and resembling fats and oils in their partition behavior in vivo into lipid phases of lipoproteins, cellular lipid droplet organelles and biological membranes. These features confer a number of unique delivery attributes in vivo, favorable to the therapy of virus infections involving cells of the lymphoid system and the liver, in particular, but these features are also favorable in general for the treatment of virus infections of man and animals.

Iminosugars and their applications

The inventors have proposed a novel panel of human plasma protein biomarkers for diagnosing hepatic fibrosis and cirrhosis. Presently there is no reliable non-invasive way of assessing liver fibrosis. A 2D-PAGE based proteomics study was used to identify potential fibrosis biomarkers. Plasma from patients with hepatic cirrhosis induced by infection with the hepatitis C virus (HCV) were analyzed. Several proteins associated with liver scarring and potentially also related to viral infection were identified. These proteins include 14-3-3 protein zeta/delta, adiponectin, afamin, alpha-1-antitrypsin, alpha-2-HS-glycoprotein, apolipoprotein C-III, apolipoprotein E, C4b-binding protein beta chain, intact/cleaved complement C3dg, corticosteroid-binding globulin, fibrinogen gamma chain, beta haptoglobin at pH 5.46-5.49, haptoglobin-related protein, hemopexin, immunoglobulin J chain, leucine-rich alpha-2-glycoprotein, lipid transfer inhibitor protein, retinol-binding protein 4, serum paraoxonase/arylesterase 1, sex hormone-binding globulin and zinc-alpha-2-glycoprotein. These biomarkers can be used in conjunction with polypeptides in WO/2008/031051. The concentrations of these novel biomarkers can be determined using an immunoassay where the concentrations would reflect the extent of fibrosis. A fibrosis scoring scale for each of the novel biomarkers is proposed. The additive result from the scores of all the novel biomarkers would give a more reliable indication of the degree of fibrosis rather than examining individual biomarkers.

Clinical diagnosis of hepatic fibrosis using a novel panel of low abundant human plasma protein biomarkers

Provided are novel methods of treating and/or preventing a disease or condition caused by or associated with a virus belonging to the Togaviridae family using iminosugars, such as DNJ derivatives.

Iminosugars and methods of treating togaviral diseases

Provided are methods of reducing cellular cholesterol levels using lipid particles that are capable of cellular entry. Such lipid particles may be used for treating or preventing a disease or condition that is caused by or associated with an increased cellular cholesterol level and for treating or preventing a disease or condition, that is caused by or associated with a virus, that relies on cellular cholesterol for its replication.

Cholesterol level lowering liposomes

Provided are novel methods of treating and/or preventing a disease or condition caused by or associated with a virus belonging to the Bunyaviridae or Togaviridae family using iminosugars, such as DNJ derivatives.

Iminosugars and methods of treating bunyaviral and togaviral diseases

One can identify and quantify one or more glycosylation markers of a physiological condition such as a disease or a stage of disease by utilizing quantitative HPLC analysis of glycans which have been released from unpurified glycoproteins. The unpurified glycoproteins can be total glycoproteins or a selection of the total glycoproteins. The identified glycosylation marker can be a native glycan or a digestion product which has been segregated and amplified by exoglycosidase digestions. This strategy is compatible with a high throughput format and glycan data base searching. One can utilize the identified glycosylation marker, for example, for monitoring the physiological condition in a subject. One can also use the glycosylation marker to identify glycoproteins that carry the glycosylation marker which can also be used to monitor the physiological condition. The biomarker may also be a subset of glycoforms of a glycoprotein that are separated in trains of spots on 2D gel.

Automated strategy for identifying physiological glycosylation markers(s)

Growing community of inventors

Oxford, United Kingdom

Nicole Zitzmann