The Hospital for Sick Children

Mcmaster University

Hsc Research and Development Limited Partnership

University of Manitoba

Don J Mahuran

Eric Brown

Michael B Tropak

Jan E Blanchard

Justin D Buttner

Brian Mark

Denis Reynaud

Brigitte Rigat

Joe T R Clarke

John W Callahan

Eric D Brown

Therapeutic compositions and methods for treatment of late-onset Gaucher disease are described herein. The compositions comprise compounds having activity as pharmacological chaperones for mutant forms of the beta-glucocerebrosidase. Methods of treatment involve providing therapeutically effective amounts of such compositions to subjects in need thereof.

Method for enhancing folding and transport of misfolded glucocerebrosidase

Embodiments herein include variants of &#x3b2;-hexosaminidase that are useful for hydrolyzing GM2 ganglioside, polynucleotides encoding the same, and related methods. In various embodiments, a variant &#x3b2;-hexosaminidase subunit is included wherein the variant &#x3b2;-hexosaminidase subunit forms a homodimer under physiological conditions and wherein the variant &#x3b2;-hexosaminidase subunit associates with Gactivator protein to hydrolyze Gganglioside. In some embodiments, an isolated or recombinant polynucleotide encoding such a variant &#x3b2;-hexosaminidase subunit is included. In some embodiments, a method of treating a subject exhibiting an abnormal cellular accumulation of GM2 ganglioside is included wherein the method includes administering a composition including a protein variant of &#x3b2;-hexosaminidase or a polynucleotide encoding the same. Other embodiments are included herein.

&#x3b2;-hexosaminidase protein variants and associated methods for treating GM2 gangliosidoses

Methods of treating Parkinson's disease

Methods of treating lysosomal storage disorders

Method of treating Gaucher disease

Method of treating gaucher disease

A method is provided for determining the activity of an enzyme which releases methylumbelliferone (MU) from an MU-containing substrate wherein the enzyme has a pH optimum below the pKa of MU comprising: contacting a sample suspected of containing the enzyme with the MU-containing substrate at a pH suitable for activity of the enzyme to allow release of MU by the enzyme; contacting the sample with light of a wavelength in the range of about 310 nm to about 350 nm; determining fluorescence produced by the released MU, thereby determining the activity of the enzyme. This real time method provides improved diagnostic methods, for example for diseases associated with an abnormal level of activity of a glycosidase. The real time assay also can be used to screen compounds for their ability to modulate enzyme activity using MU-containing substrates.

Real time methylumbelliferone-based assay

The invention relates to products and methods for medical treatment of Gaucher disease and, in particular, an improved Gcc DNA for insertion into any applicable expression vector for gene therapy treatment. The invention includes an isolated Gcc DNA molecule, wherein nucleic acid molecules have been modified at cryptic splice sites to prevent or decrease splicing of mRNA produced from the DNA molecule, while preserving the ability of the DNA to express functional Gcc polypeptides.

Products and methods for gaucher disease therapy

An anti-inflammatory composition is provided. The composition comprises GM activator protein or a peptide derived from the GM activator protein which is capable of inhibiting platelet activating factor (PAF). The composition is useful in the treatment of inflammatory conditions such as inflammatory bowel disease and asthma.

Inhibitor of platelet activating factor

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Toronto, Canada

Don J Mahuran