University of Washington

Other

Novartis Ag

Schering Corporation

Sandoz Gmbh

The Brigham and Women's Hospital, Inc.

Case Western Reserve University

The University of North Carolina at Chapel Hill

Perkinelmer Health Sciences, Inc.

UniversitÈ Laval

Institute for Systems Biology

Revvity Health Sciences, Inc.

Hérma-Québec

Michael H Gelb

Frantisek Turecek

C Ronald Scott

Sophie Blanchard

Rudolf Hans Aebersold

Beate Rist

Zdenek Spacil

Steven P Gygi

Scott A Gerber

Mariana Natali Barcenas Rodriguez

Paul Yager

Frances Meredith Hocutt

John Robert Gillespie

Eric Boilard

Frederick Simmons Buckner

Alex S Goldstein

Arun Babu Kumar

Anatoly N Lukyanov

Alexander Cherkassky

Richard Ray Tidwell

Valentina Molteni

Arnab Kumar Chatterjee

Corey Strickland

Mary L Disis

Patricia C Weber

Advait Suresh Nagle

Fang Liang

William T Windsor

Casey Jacob Nelson Mathison

Frantisek Supek

Liying Jocelyn Tan

Neil Norcross

Pranab Kumar Mishra

Howard Hindin

James E Bollinger

Agnes Vidal

David M Lee

Donald Alan Patrick

Reuben Gobezie

Louis Thibault

Jason Coumoyer

Hari Babu Tatipaka

Daniel Gedder Silva

Patricia Q Bottari

Robert H Abeles

Paul A Carlson

Kyujin C Lee

Sophia M B Masi

Luc Boudreau

Jason Cournoyer

Adenek Spacil

Provided are molecules and methods for detecting enzymatic activity of various lysosomal storage enzymes. The molecules may be used as internal standards that may be combined with substrates that have improved solubility.

Compounds and methods relating to lysosomal storage disorders

Reagents, methods, and kits for assaying enzymes associated with lysosomal storage diseases MPS-I, MPS-II, MPS-IIIA, MPS-IIIB, MPS-IVA, MPS-VI, and MPS VII.

Reagents and methods for screening MPS I, II, IIIA, IIIB, IVA, VI, and VII

An oral appliance and kit therefor is disclosed. The oral appliance may include generally U-shaped upper and lower body members and a pair of adjustment plates or spacers for removably connecting the upper body member with the lower body member. The generally U-shaped upper and lower body members are adapted to be positioned over at least a portion of first and second arches of teeth, respectively, with the spacers having a system of pins or pegs for adjustably repositioning the upper body member with respect to the lower body member. The upper and lower body members are further configured to provide a lingual-less open space between the upper and lower body members to accommodate a tongue in a relaxed state. The disclosed oral appliance, system and kit therefor is configured for use in correcting the misalignment of a user's jaw.

Apparatus and kit for an oral appliance and method for using same

Lysosomal acid lipase (LAL) substrates, assays for lysosomal acid lipase using the substrates, and methods for diagnosing diseases and conditions attributable to lysosomal acid lipase deficiency.

Lysosomal acid lipase assay

Methods are provided for detecting enzymatic activity of various lysosomal storage enzymes using substrates that include: a sugar moiety; a linker moiety allowing the conjugation of sugar moiety with the remaining structure of the substrate; and two or more fatty acid chains or derivatives thereof at least one of which is sufficiently structured to provide improved solubility in aqueous or organic solvent systems. Also provided are internal standards, and inhibitors for use in detecting or reducing enzymatic activity using the inventive substrates.

The present disclosure provides assays for lysosomal enzymes, specifically palmitoyl protein thioesterase 1 (PPT1) and tripeptidyl peptidase 1 (TPP1), using, for example, tandem mass spectrometry. The assays involve the detection of enzymatic products obtained through the action of the lysosomal enzymes on new enzyme substrates, and can be used for quantitative enzyme activity measurements. The assays for the enzymes utilize a minimum steps for sample work up and can be run in a simplex format or in a duplex format for the detection of neuronal ceroid lipofuscinoses, or in a multiplex format with other mass spectrometry-based assays for screening of neuronal ceroid lipofuscinoses and other lysosomal storage disorders.

Methods for assaying palmitoyl protein thioesterase 1 and tripeptidyl peptidase activity in dried blood spots for detection of neuronal ceroid lipofuscinoses in newborns

The present invention relates to novel compounds that cross the blood-brain barrier and are effective inhibitors of neurological pathogens such as trypanosomes. The invention further relates to the use of these compounds for treating disorders related to trypanosomes and neurological pathogens.

Compounds for treatment of trypanosomes and neurological pathogens and uses thereof

Reagents, methods, and kits for assaying enzymes associated with lysosomal storage diseases MPS-I, MPS-II, MPS-IIIA, MPS-IIIB, MPS-IV A, MPS-VI, and MPS VII. In one aspect, the invention provides methods for assaying one or more enzymes associated with a lysosomal storage disease. In a first embodiment, the method includes: (a) contacting a sample with a first solution to provide a solution comprising one or more lysosomal enzymes; (b) contacting the one or more lysosomal enzymes in solution with an enzyme substrate for each lysosomal enzyme to be analyzed and incubating the substrates with the enzymes for a time sufficient to provide a solution comprising an enzyme product for each lysosomal enzyme present in the sample.

The present disclosure highlights the relationship between extracellular mitochondrial components, optionally in combination with the secreted phospholipase A-IIA and/or an auto-antibody, and in vivo as well as in vitro and inflammatory reactions/conditions, especially those released as a result of the degradation of a platelet. The present disclosure provides methods for determining the presence of inflammatory mediators, for limiting inflammatory reactions/conditions, for the diagnosis inflammatory reactions/conditions, for screening therapeutics for the treatment and/or the alleviation of symptoms of inflammatory reactions/conditions based on the detection or modulation of the level of these extracellular mitochondrial components.

Extracellular mitochondrial components for detecting inflammatory reactions and conditions

Methods for assaying &#x3b1;-L-iduronidase enzymatic activity and methods for screening newborns for Mucopolysaccharidosis Type-I.

Methods for assaying alpha-L-iduronidase enzymatic activity

Methods and liquid compositions for assaying the activity of one or more lysosomal enzymes in a sample are provided. In some embodiments, the assay is a multiplexed assay for the activities of a plurality of lysosomal enzymes in the sample. The compositions and methods can comprise or employ: one or more metal cations effective for precipitating sulfate ions, one or more metal cations effective for precipitating phosphate ions, a maltase glucoamylase inhibitor, a beta-N-acetylhexosaminidase inhibitor, and one or more surfactants.

Methods and compositions for assaying the activity of one or more lysosomal enzymes

Method for selective 2-sulfation of glycosides.

Method for 2-sulfation of glycosides

The present invention provides compounds of formula I: or a pharmaceutically acceptable salt, tautomer, or stereoisomer, thereof, wherein the variables are as defined herein. The present invention further provides pharmaceutical compositions comprising such compounds and methods of using such compounds for treating, preventing, inhibiting, ameliorating, or eradicating the pathology and/or symptomology of a disease caused by a parasite, such as Leishmaniasis, Human African Trypanosomiasis and Chagas disease.

Compounds and compositions for the treatment of parasitic diseases

Method and reagent for converting a carboxylic acid to a positively charge amide are described. The method and reagent facilitate positive ion mass spectral analysis of carboxylic acids. The method includes reacting a carboxylic acid with a compound having formula I: wherein A and B are aromatic rings, ring A includes a quaternized nitrogen and has n additional ring atoms, each additional ring atom optionally substituted with an Rgroup, and n is an integer from 4 to 10, and ring B includes a carbon atom and has m additional ring atoms, each additional ring atom optionally substituted with an Rgroup, and m is an integer from 4 to 10. The compound includes at least one Ror Rgroup, and the at least one Rand Rgroup is -L-N(Z)H; and Xis a counterion.

Reagent and method for detection of carboxylic acids by mass spectrometry

Methods for assaying &#x3b1;-L-iduronidase enzymatic activity

Growing community of inventors

Seattle, WA, United States of America

Michael H Gelb