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

The Brigham and Women's Hospital, Inc.

The United States of America As Represented by the Department of Health

Ivan J Fuss

Warren Strober

Atsushi Kitani

Richard S Blumberg

Frank Heller

Peter Mannon

Raj K Puri

Koji Kawakami

Kazuhiko Nakamura

Brian L Kelsall

Markus F Neurath

Stefan Fichtner-Feigl

Tomohiro Watanabe

Jan Preiss

Warren Stober

Tetsuya Takagawa

Monica Boirivant

Markus Neurath

Stefan Universität Regensburg Abteilung Für Chirurgie Fichtner-Feigl

Raj Puri

Disclosed are methods of treating or preventing an intestinal disease or disorder comprising administering to a subject a modulator of leucine rich repeat kinase 2 (LRRK2) in an amount effective to treat or prevent an intestinal disease or disorder and methods of determining the susceptibility or risk of a subject to develop an intestinal disease.

Treatment or prevention of an intestinal disease or disorder

The present invention provides a method of treating or preventing the inflammatory response of ulcerative colitis or Crohn's disease in a subject comprising administering to the subject an effective amount of a substance that inhibits the binding of IL-13 to IL-13 receptors on NKT cells or delivers an effector molecule to the NKT cells.

Methods of treating and preventing inflammatory bowel disease involving IL-13 and NKT cells

Method of treating or preventing the inflammatory response of colitis in a subject comprising administering to the subject an effective amount of a substance that modulates IL-13 activity (FIG.). The invention also provides a method of treating or preventing the inflammatory response of colitis in a subject comprising administering to the subject an effective amount of a substance that modulates NK-T cell activity. The invention also provides for the screening of substances that treat or prevent the inflammatory response of colitis.

Methods of treating and preventing colitis involving IL-13 and NK-T cells

The present invention provides a method of treating or preventing inflammation in a subject comprising administering to the subject an effective amount of a muramyl dipeptide (MDP).

Use of muramyl dipeptide (MDP) for treating inflammation

Methods of treating colitis involving IL-13 and NK-T cells

The present invention provides alternatives to traditional drug and surgical treatments for IBD. In particular, the present invention provides compositions and methods for the treatment of autoimmune diseases such as IBD in humans using TGF-&#x3b2; therapy. The compositions of the present invention provide vectors containing TGF-&#x3b2; under the control of an inducible promoter. In particularly preferred embodiments, the present invention provides regulated plasmid constructs capable of inducing TGF-&#x3b2; production. In preferred embodiments, the methods of the present invention utilize the vectors described for assaying the expression of a gene in a cell. In some preferred embodiments, the methods of the present invention utilize the administration of TGF-&#x3b2; containing vectors to treat IBD. In alternative preferred embodiments, the present invention provides methods and compositions for the induction of high-level interleukin (e.g., IL-10) production.

Inducible plasmid vector encoding TGF-&#x3b2; and use thereof

The present invention provides a method of treating or preventing inflammation in a subject, comprising administering to the subject an effective amount of cholera toxin subunit B. The present invention also provides a method of decreasing the activity of interferon gamma in a subject, comprising administering to the subject an effective amount of cholera toxin subunit B. Further provided is a method of decreasing the activity of IL-12 in a subject, comprising administering to the subject an effective amount of cholera toxin subunit B. Additionally, the present invention provides a method of treating or preventing a Th1 T-cell mediated autoimmune disorder in a subject, comprising administering to the subject an effective amount of cholera toxin subunit B.

Methods of treating inflammatory bowel disease using cholera toxin B subunit

The present invention provides a method of treating or preventing the inflammatory response of an inflammatory bowel disease in a subject, comprising administering to the subject an amount of a STAT-4 antisense oligonucleotide effective in treating or preventing the inflammatory response of the inflammatory bowel disease.

Methods of treating colitis using STAT-4 anti-sense oligonucleotides

The present invention provides a method for treating the inflammatory response of an established colitis in a subject with inflammatory bowel disease (IBD), comprising administering to a subject diagnosed with an established colitis from an IBD an amount of an antibody to interleukin-12 effective in reducing the colitis-inducing effect of interleukin-12. Also provided is a method for screening a substance for its effectiveness in reducing the inflammatory response of an established colitis comprising obtaining an animal having an established colitis; administering the substance to an animal; and assaying the animal for an effect on interleukin-12 which results in the reduction of the inflammatory response of the colitis, an amount of reduction of the inflammatory response greater than the amount of reduction produced by the administration of antibodies against interferon-gamma or tumor necrosis factor-alpha indicating an effective substance. Additionally, the present invention provides a method for screening a substance for its effectiveness in preventing inflammatory bowel disease comprising administering the substance to an animal susceptible to colitis; subjecting the animal to a treatment that will induce a colitis; assaying the animal for the development of a colitis; and comparing the effectiveness of the substance in preventing development of a colitis to the effectiveness of antibodies to interferon-gamma or tumor necrosis factor-alpha in preventing development of a colitis, a substance more effective in preventing the development of a colitis than antibodies to interferon-gamma or tumor necrosis factor-alpha indicating an effective substance.

Methods of treating established colitis using antibodies against IL-12

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Bethesda, MD, United States of America

Ivan J Fuss