Mount Sinai School of Medicine

Amicus Therapeutics, Inc.

Pfantastic Medical Research Institute, LLC

Icahn School of Medicine at Mount Sinai

Universitéde Montreal

New York University

Jian-Qiang Fan

Satoshi Ishii

Naoki Asano

Gary Lee

Kenneth Valenzano

Michel Bouvier

Robert J Desnick

Kamlesh A Sheth

Kamlesh Sheth

Patricia René

Xiaoxiang Zhu

Ken Vanlenzano

Patricia Rene

Patricia RenÉ

Satoshi Ishi

The invention relates to methods of enhancing normal melanocortin-4 receptor (MC4R) activity, and to enhancing activity of an MC4R having a mutation which affects protein folding and/or processing of the MC4R. The invention provides a method of treating an individual having a condition in which increased activity of an MC4R at the cell surface would be beneficial, for example in obesity, by administering an effective amount of a pharmacological chaperone for the MC4R. The invention provides MC4R pharmacological chaperones which enhance the activity of MC4R. The invention further provides a method of screening to identify pharmacological chaperones which enhance folding of an MC4R in the endoplasmic reticulum (ER), in order to enhance the activity of the MC4R at the cell surface.

Pharmacological chaperones for treating obesity

This application provides methods of improving protein replacement therapy by combining protein replacement therapy with active site-specific chaperones (ASSC) to increase the stability and efficiency of the protein being administered. The application further provides stable compositions comprising the purified protein and an ASSC, and methods of treatment by administering the compositions.

Stable formulations of purified proteins

The present invention relates to methods for treating obstructive sleep apnea (OSA), alleviating a negative OSA symptom, reducing snoring, or improving quality of life in a subject, comprising administering to the subject an effective amount of a pharmaceutical composition comprising pyridostigmine before sleep. Also provided are related medicaments as well as methods for preparing the medicaments.

Methods for treating obstructive sleep apnea

A method of enhancing the activity of lysosomal &#x3b1;-Galactosidase A (&#x3b1;-Gal A) in mammalian cells and for treatment of Fabry disease by administration of 1-deoxy-galactonojirimycin and related compounds.

Method of enhancing lysosomal &#x3b1;-galactosidase A

Method for enhancing in a mammalian cell the activity of an enzyme associated with Gaucher Disease by administering a competitive inhibitor of glucocerebrosidase in an amount effective to enhance the activity of the enzyme. Preferred compounds for use in the method are imino sugars and related compounds. In particular, C8-12-alkyl derivatives of N-alkyl-deoxynojirimycin, isofagomine compounds, and calystegine compounds are effective to enhance glucocerebrosidase activity.

Method for increasing the activity of lysosomal enzymes

Method for enhancing in a mammalian cell the activity of an enzyme associated with Gaucher Disease by administering a competitive inhibitor of glucocerebrosidase in an amount effective to enhance the activity of the enzyme. Preferred compounds for use in the method are imino sugars and related compounds. In particular, C8-12-alkyl derivatives of N-alkyl-deoxynojirimycin, isofagomine compounds, and calystegine compoiunds are effective to enhance glucocerebrosidase activity.

Method for increasing the activity of acid-&#x3b2;-galactosidase

The present invention provides novel hydroxy piperidine (HP) derivatives having (i) a positive charge at the position corresponding to the anomeric position of a pyranose ring; (ii) a short, flexible linker emanating from the corresponding position of the ring oxygen in a pyranose; and (iii) a lipophilic moiety connected to the linker and pharmaceutically acceptable salts thereof. The linker can be absent if the lipophilic moiety corresponds to a hydrocarbon chain with a linear length of 6 or more carbons. The present invention further provides a method for treating individuals having Gaucher disease by administering the novel HP derivative as 'active-site specific chaperones' for the mutant glucocerebrosidase associated with the disease.

Hydroxy piperidine derivatives to treat gaucher disease

Provided is a method for enhancing the activity of a protein, which protein when mutated, folds in an incorrect conformation in the endoplasmic reticulum, by contacting the protein with an effective amount of a compound which specifically binds to the protein and induces the protein to fold into a proper conformation (a specific chaperone). Also provided are methods for enhancing the stability and preventing the degradation of a protein by contacting the protein with an effective amount of a specific chaperone for the protein which stabilizes the protein in a proper conformation.

Method for enhancing mutant protein activity

This application provides methods of improving gene therapy by combining gene therapy with active site-specific chaperones (ASSCs). The ASSC increases the stability and efficiency of the protein encoded by the recombinant gene that is administered.

Combination therapy for treating protein deficiencies

Method for enhancing in a mammalian cell the activity of an enzyme associated with Gaucher Disease by administering a competitive inhibitor of glucocerebrosidase in an amount effective to enhance the activity of the enzyme. Preferred compounds for use in the method are imino sugars and related compounds. In particular, C8&#x2013;12-alkyl derivatives of N-alkyl-deoxynojirimycin, isofagomine compounds, and calystegine compounds are effective to enhance glucocerebrosidase activity.

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Demarest, NJ, United States of America

Jian-Qiang Fan