The Feinstein Institutes for Medical Research

The General Hospital Corporation

University of Pittsburgh

Huan Yang

Kevin J Tracey

Yousef Al-Abed

Mitchell P Fink

Howland Shaw Warren

Methods of treating HMGB1-mediated inflammation by administering a therapeutically effective amount of an MD2-antagonist to a subject in need thereof are described. The novel MD2 antagonist tetrapeptide P5779 is also described.

Treatment of HMGB1-mediated inflammation

The present invention is related to HMGB1 antagonists and, in particular, HMGB1 tetramer peptidomimetics which have been stabilized with at least one azatide linkage, such as K883. The present invention is also related to pharmaceutical compositions comprising HMGB1 antagonists such as K883.

HMGB1 antagonist

The present invention is related to the use of HMGB1 antagonists, specifically derivatives of K883 in the treatment and/or prevention and/or inhibition of neuropathy pain, and in particular diabetic neuropathy in mammals, e.g., humans, and pharmaceutical compositions for the same comprising HMGB1 antagonists in an effective amount to treat and/or prevent and/or inhibit this condition.

HMGB1 antagonist treatment of diabetic peripheral neuropathy

Compositions and methods are disclosed for inhibiting the release of a proinflammatory cytokine from a vertebrate cell, and for inhibiting an inflammatory cytokine cascade in a patient. The compositions comprise a vertebrate HMGB A box, and an antibody preparation that specifically binds to a vertebrate HMGB B box. The methods comprise treating a cell or a patient with sufficient amounts of the composition to inhibit the release of the proinflammatory cytokine, or to inhibit the inflammatory cytokine cascade.

Antibodies to high mobility group-1(HMGB1) B-box polypeptides

The invention features a method of treating an inflammatory condition in an individual, comprising administering an agent inhibits the interaction between a Toll-like receptor 2 (TLR2) and a high mobility group B (HMGB) polypeptide to the individual. The invention also features methods for identifying agents that inhibit the interaction between TLR2 and HMGB.

Inhibitors of the interaction between HMGB polypeptides and toll-like receptor 2 as anti-inflammatory agents

Use of HMGB fragments as anti-inflammatory agents

The invention features a method of treating an inflammatory condition in an individual, comprising administering an agent that inhibits the interaction between a Toll-like receptor 2 (TLR2) and a high mobility group B (HMGB) polypeptide to the individual. The invention also features methods for identifying agents that inhibit the interaction between TLR2 and HMGB.

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Douglaston, NY, United States of America

Huan Yang