Genetics Institute, Inc.

Genzyme Corporation

Other

Wyeth

John P Leonard

Samuel Goldman

Richard O'Hara, Jr

Seng H Cheng

Bradford Hirth

Thomas A Natoli

Elyse Bourque

Elina Makino

Nelson S Yew

James W Lillie

Hanlan Liu

Oxana Ibraghimov-Beskrovnaya

Paul Mason

Mary A Cromwell

Bing Wang

Lingyun Li

Thomas O'Shea

Fazeela Morshed

Renato Sklerj

Andrew Charles Good

Renato Skerlj

John Marshall

Yibin Xiang

Cassandra Celatka

Ronald K Scheule

Markus Metz

Beatriz M Carreno

Zhong Zhao

Oxana Beskrovnaya

Herve Husson

Katherine Jancsics

Mario A Cabrera-Salazar

Cécile Orsini

Sandra Viale

Gwénaëlle Ret-lecuelle

Gwenaelle Ret-Lecuelle

Richard O'hara

Oxana Ibraghinov-Beskrovnaya

The invention relates to inhibitors of glucosylceramide synthase (GCS), such as Compound of Formula I, shown below, as defined herein, useful for the treatment of metabolic diseases, such as lysosomal storage diseases, either alone or in combination with enzyme replacement therapy, cystic disease and for the treatment of cancer. 

Glucosylceramide synthase inhibitors

A method of treating polycystic kidney disease in a subject comprises administering to the subject an effective amount of a compound represented by Structural Formula (1): or a pharmaceutically acceptable salt thereof.

Method of treating polycystic kidney diseases with ceramide derivatives

The invention relates to inhibitors of glucosylceramide synthase (GCS) useful for the treatment metabolic diseases, such as lysosomal storage diseases, either alone or in combination with enzyme replacement therapy, and for the treatment of cancer.

A method of treating polycystic kidney disease in a subject comprises administering to the subject an effective amount of a compound represented by Structural Formula (1): or a pharmaceutically acceptable salt thereof. 

Method of treating autoimmune conditions are disclosed comprising administering to a mammalian subject IL-12 or an IL-12 antagonist. In certain preferred embodiments the autoimmune condition is one which is promoted by an increase in levels of IFN-&#x3b3; or TNF-&#x3b1;. Suitable conditions for treatment include multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, autoimmune pulmonary inflammation, Guillain-Barre syndrome, autoimmune thyroiditis, insulin dependent diabetes melitis and autoimmune inflammatory eye disease.

Use of IL-12 and IL-12 antagonists in the treatment of autoimmune diseases

Disclosed are methods for downmodulating an immune response comprising contacting an immune cell with an agent that modulates the interaction between PD-1 and a PD-1 ligand (e.g., soluble forms of PD-1 or PD-1 ligand or antibodies to PD-1) to thereby modulate the immune response.

Methods for downmodulating immune cells using an antibody to PD-1

Method of treating autoimmune conditions are disclosed comprising administering to a mammalian subject IL-12 or an IL-12 antagonist. In certain preferred embodiments the autoimmune condition is one which is promoted by an increase in levels of IFN-&ggr; or TNF-&agr;. Suitable conditions for treatment include multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, autoimmune pulmonary inflammation, Guillain-Barre syndrome, autoimmune thyroiditis, insulin dependent diabetes melitis and autoimmune inflammatory eye disease.

Use of IL-12 antagonists in the treatment of rheumatoid arthritis

Use of IL-12 antagonists in the treatment of conditions promoted by an increase in levels of IFN-y

Growing community of inventors

Manchester, NH, United States of America

John P Leonard