The State University of New York

University of Miami

Hospital for Joint Diseases

Other

Nungavaram S Ramamurthy

Lorne M Golub

Thomas F McNamara

Sanford R Simon

Norman L Block

Hsi-Ming Lee

Marie G Selzer

Balakrishna L Lokeshwar

Robert A Greenwald

Steven B Abramson

Ashok R Amin

Maria Emanuel Ryan

Howard Trachtman

Elizabeth J Roemer

Methods of reducing the risk of cataract development in a mammal are provided and include administering to the mammal an effective amount of a tetracycline derivative. A preferred tetracycline derivative administered according to the methods of the present invention is 6&#x3b1;-deoxy 5-hydroxy-4-dedimethylaminotetracycline.

Inhibitor of cataract formation

The invention is a method of inhibiting a sarcoma, such as Kaposi's sarcoma, in a mammal. The method employs 6-demethyl-6-deoxy-4-de(dimethylamino)tetracycline (CMT-3.)

Method of inhibiting cancer growth

The invention is a method of inhibiting cancer growth, by inhibiting cellular proliferation, invasiveness, or metastasis, or by inducing cytotoxicity against cancer in mammals. The method employs 6-demethyl-6-deoxy-4-de(dimethylamino)tetracycline (CMT-3) and other functionally related chemically modified, preferably non-antibacterial, tetracycline compounds to inhibit cancer growth. The method is particularly effective to inhibit the establishment, growth, and metastasis of solid tumors, such as tumors derived from colon cancer cells, breast cancer cells, melanoma cells, prostatic carcinoma cells, or lung cancer cells.

A method for treating diabetes in a mammal by moderately controlling blood glucose concentration in the mammal together with administering to the mammal an amount of a tetracycline compound effective to reduce complications associated with diabetic hyperglycemia. The method enables long term management of diabetes by avoiding the problems associated with tight control of blood glucose concentrations, i.e., hypoglycemia tolerance and seizures, while simultaneously avoiding the problems associated with conventional moderate control of blood glucose concentrations, i.e., pathological complications associated with hyperglycemia, such as nephropathy, retinopathy, etc. Blood glucose concentration can be controlled by moderate administration (e.g., fewer injections per day) of insulin or another glucose-modulating agent, while pathological complications characteristic of diabetic hyperglycemia are ameliorated through the activity of tetracycline compound, the latter preferably administered in an amount that is substantially non-antimicrobial.

Therapeutic method for management of diabetes mellitus

The invention is a method of inhibiting the production of nitric oxide (NO) in an in vivo, in vitro, or ex vivo biological system. The method employs a tetracycline compound to inhibit the production of NO and/or to inhibit the expression or activity of an inducible isoform of nitric oxide synthase (iNOS). Preferably, the tetracycline compound has inhibitory activity for metalloproteinases. Also it is preferred that the tetracycline compound is provided to the biological system in an amount which has little or no antibacterial activity in the system. Accordingly, preferred tetracycline compounds are tetracycline compounds which have be modified to reduce or eliminate their antimicrobial activity. The method can be used to treat medical conditions in mammals characterized by NO production mediated by iNOS, including, for example, inflammatory conditions.

Method for inhibiting expression of inducible nitric oxide synthase with

The invention is a method of inhibiting cancer growth, including cellular proliferation, invasiveness, or metastasis in mammals. The method employs 6-demethyl-6-deoxy-4-dedimethylaminotetracycline (CMT-3) and other functionally related chemically modified, preferably non-antibacterial, tetracycline compounds to inhibit cancer growth. The method is particularly effective to inhibit the establishment, growth, and metastasis of solid tumors, such as tumors derived from colon cancer cells, breast cancer cells, melanoma cells, prostatic carcinoma cells, or lung cancer cells.

A method for improving the healing response of epithelialized tissue (e.g., skin, mucosae) to acute traumatic injury is disclosed. The method includes employing a tetracycline compound, having substantially no antibacterial activity, to improve the capacity of the epithelialized tissue to heal acute wounds. Specifically, the method involves increasing the rate of collagen accumulation of the healing epithelialized tissue above that associated with wound healing in the individual. The method decreases proteolytic activity in the epithelialized tissue by means of the tetracycline compound, most commonly decreasing collagenolytic activity and/or decreasing gelatinolytic activity. Collagenase and gelatinase activity have been shown to be decreased by the method of the invention. Preferably, the method is employed to improve the wound healing capacity of human or animal subjects in whom such capacity is impaired. Also, the non-antibiotic tetracycline is preferably administered topically at the site of the wound.

Promotion of wound healing by chemically-modified tetracyclines

A method is disclosed for inhibiting endogenous production of nitric oxide (NO) in an in vivo, in vitro, or ex vivo mammalian system. The method employs a tetracycline compound to inhibit production of NO and/or to inhibit the expression or activity of an inducible isoform of nitric oxide synthase (iNOS). Preferably, the tetracycline compound has inhibitory activity for metalloproteinases. Also it is preferred that the tetracycline compound is provided to the mammalian system in an amount which has little or no antibacterial activity in the system. Accordingly, preferred tetracycline compounds are tetracycline compounds which have be modified to reduce or eliminate their antimicrobial activity. The method can be used to treat medical conditions in mammals characterized by NO production mediated by iNOS, including, for example, inflammatory conditions.

Method of using tetracycline compounds for inhibition of endogenous

A method for inhibiting the activity of serine proteinase in biological systems includes administering to the system a serine proteinase inhibitory amount of a hydrophobic 4-de(dimethylamino)tetracycline. The method reduces tissue destruction during inflammation resulting from the activity of human leukocyte elastase. The method is used for pharmaceutical and cosmetic purposes.

Serine proteinase inhibitory activity by hydrophobic tetracycline

Tetracyclines having substantially no effective antibiotic or antibacterial activity and possessing anti-collagen-destructive enzyme activity or anti-collagenase activity and compositions containing the same have been found useful as anti-collagenolytic agents. Such tetracyclines and compositions containing the same are useful in the treatment of periodontal diseases, corneal ulcers, bone deficiency disorders, rheumatoid arthritis diseases characterized by excessive collagen destruction. A special aspect of this invention involves the incorporation of such tetracyclines in animal feed compositions for improved animal nutrition, such as may be evidenced by increased weight gain.

Non-antibacterial tetracycline compositions possessing

Tetracyclines, antibacterial and non-antibacterial tetracyclines, have been found to be useful in the treatment of osteoporosis in humans by administering to the human suffering from osteoporosis an effective amount of a tetracycline to enhance bone protein synthesis. Tetracyclines which have been found to be effective in the treatment of osteoporosis in humans include minocycline, doxycycline and dedimethylaminotetracyline.

Growing community of inventors

Smithtown, NY, United States of America

Nungavaram S Ramamurthy