The Brigham and Women's Hospital, Inc.

Ortho-mcneil Pharmaceutical Corp.

Romana A Nowak

Stephen S Palmer

Elizabeth A Stewart

This invention provides methods of treating a subject suffering from a leiomyoma which comprise administering to the subject a therapeutically effective amount of an agent, or alternatively a plurality of agents, which inhibit specific metalloproteinases. This invention further provides diagnostic methods of determining whether a tumor in a subject is a leiomyoma. This invention further provides pharmaceutical compositions and kits for practicing the instant methods. Finally, this invention provides a method of determining whether an agent specifically inhibits certain metalloproteinases.

Methods and kits for treating and diagnosing leiomyomas

The invention provides methods for treating abnormal uterine bleeding via application of compounds that block uterine stromal cell response to angiogenic growth factors by interfering with the growth factors themselves, by blocking receptors in the uterine epithelial or stromal cells to those growth factors, and/or by inhibiting other receptors to those growth factors. The compounds include interferons, particularly type I interferons, pirfenidone, heparin, heparin-like polyaromatic anionic compounds, heparin-sulfate-based compounds, secreted or soluble FGF receptors, and/or RGD-peptide. The angiogenic growth factors to which response is blocked include basic fibroblast growth factor (bFGF), FGF receptors (FGFR), acidic fibroblast growth factor (aFGF), transforming growth factor &bgr; (TGF-&bgr;), platelet-derived growth factor (PDGF), heparin binding epidermal growth factor (HBEGF), vascular endothelial growth factor (VEGF), parathyroid hormone-related protein (PTHrP) and/or prolactin. The methods contemplate introducing the aforementioned response-blocking compounds into the body of a patient either systemically, e.g., via injection or implant, or locally to the uterus, e.g., via medicated intrauterine devices, foams and the like. The invention also provides methods for female contraception comprising administering the aforementioned response-blocking compounds, along with progestin or a progestin-only contraceptive, to inhibit pregancy while reducing bleeding otherwise associated with such contraceptives.

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West Roxbury, MA, United States of America

Romana A Nowak