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

The General Hospital Corporation

University of Kansas

The Ml4 Foundation

Ehud Goldin

Wei Ping Zheng

Juan Jose Marugan

Noel Terrence Southall

Samarjit Patnaik

Wendy Westbroek

Ellen Sidransky

Omid Motabar

Frank John Schoenen

Steven Andrew Rogers

Susan A Slaugenhaupt

David F Moore

Alison E Baird

Mei Sun

James S Acierno, Jr

Elma Aflaki

Wei Zheng

Wendy Westbrook

Noel Southall

Substituted pyrazolopyrimidines and dihydropyrazolopyrimidines and related compounds, their methods of manufacture, compositions containing these compounds, and methods of use of these compounds in treating lysosomal storage disorders such as Gaucher disease are described herein. The compounds are of general Formula (I) in which variables R-Rand X are described in the application.

Substituted pyrazolopyrimidines as glucocerebrosidase activators

Compounds of Formula (I) and the pharmaceutically acceptable salts thereof are disclosed. The variables. R-R, m, n, o, and p are disclosed herein. The compounds are useful for treating Gaucher disease and inhibiting the onset of Gaucher disease symptoms in a patient having a GBA gene mutation and for treating Parkinson's disease. Pharmaceutical compositions containing compounds of Formula (I) and methods of treatment comprising administering compounds of Formula (I) are also disclosed. 

Salicylic acid derivatives useful as glucocerebrosidase activators

Methods are provided for evaluating a stroke, for example for determining whether a subject has had an ischemic stroke, determining the severity or likely neurological recovery of a subject who has had an ischemic stroke, and determining a treatment regimen for a subject who has had an ischemic stroke, as are arrays and kits that can be used to practice the methods. In particular examples, the method includes screening for expression in ischemic stroke related genes (or proteins), such as white blood cell activation and differentiation genes (or proteins), genes (or proteins) related to hypoxia, genes (or proteins) involved in vascular repair, and genes (or proteins) related to a specific peripheral blood mononuclear cell (PBMC) response to the altered cerebral microenvironment. Also provided are methods of identifying one or more agents that alter the activity (such as the expression) of an ischemic stroke-related molecule.

Differential expression of molecules associated with acute stroke

The present invention relates to identification of a gene that is inactivated in a mucolipidosis condition. In particular, the invention concerns mutations that disrupt a mucolipin, preferably MCOLN1, in mucolipidosis IV. Recombinant nucleic acids encoding mutant forms of MCOLN1, oligonucleotides specific for such mutations, and diagnostic and therapeutic applications related to these discoveries, are also contemplated.

Gene encoding a new TRP channel is mutated in mucolipidosis IV

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Rockville, MD, United States of America

Ehud Goldin