The Rockefeller University

Albert Einstein College of Medicine

Other

Psorx, L.l.c.

Michael A Brownlee

Anthony Cerami

Peter C Ulrich

Helen Vlassara

Geoffrey C Gurtner

Howard J Federoff

Shimon Efrat

Marshall S Horwitz

Sandor Pongor

Hans-Peter Hammes

One aspect of the present invention relates to a method of treating or preventing pathologic effects of hyperglycemia and/or increased fatty acid flux in a subject in need of such treatment or preventive therapy. This method involves administering a composition containing a therapeutically effective amount of a ROS inhibitor to a subject in need thereof.

Method of treating or preventing pathologic effects of acute increases in hyperglycemia and/or acute increases of free fatty acid flux

One aspect of the present invention relates to a method of treating or preventing pathologic sequelae of acute hyperglycemia and/or increased fatty acid flux in a subject. This method involves administering an ROS inhibitor to the subject. In addition, methods of promoting neovascularization, inhibiting oxidation or excessive release of free fatty acids, and identifying compounds suitable for treatment or prevention of ROS-mediated injury are also disclosed.

The invention provides a method and vectors to express a gene or genes, derived from a virus, which block allograft rejection. One class of genes blocks the intracellular transport and/or intracellular maturation within the cells of proteins called MHC class I products. Without limitation as to theory, it is believed that blocking the appearance of this class of proteins on the transplanted cell's surface, prevents the host's immune system from rejecting the graft. Another class of proteins acts to permit TNF &agr;-mediated cell cytolysis. In one embodiment, the invention is directed towards engrafting the cells that secrete insulin, which are called alternatively, pancreatic &bgr;-cells and islet cells, and thereby provide a treatment of diabetes mellitus.

Attenuation of rejected cells transformed with adenovirus E3

The invention provides a cells which express a gene or genes, derived from the adenovirus E3 region, which block allograft rejection. One class of genes blocks the intracellular transport and/or intracellular maturation within the cells of proteins called MHC class I products. Without limitation as to theory, it is believed that blocking the appearance of this class of proteins on the transplanted cell's surface, prevents the host's immune system from rejecting the graft. Another class of proteins acts to permit TNF .alpha.-mediated cell cytolysis. In one embodiment, the invention is directed towards engrafting the cells that secrete insulin, which are called alternatively, pancreatic .beta.-cells and islet cells, and thereby provide a treatment of diabetes mellitus.

Pancreatic .beta.-cells for allogeneic transplantation without

The present invention relates to methods for inhibiting protein aging. Accordingly, methods are disclosed for treating an animal to inhibit the formation of advanced glycosylation end products of target proteins with the animal by adminstering a pharmaceutical composition comprising an agent capable of reacting with the carbonyl moiety of the early glycosylation product, whereby the subsequent cross-linking of the early glycosylation product is inhibited. Agents of the present invention comprise aminoguanidine, its pharmaceutically acceptable salts, and mixtures thereof.

Methods for inhibiting the advanced glycosylation of proteins

Methods and a compositions are provided for treating a skin proliferation disease such as psoriasis to inhibit the proliferation of epidermal cells, particularly keratinocytes and to reduce the symptoms of erythematous scales associated with the disease. The method comprises administering to a mammalian host with a skin proliferation disease a composition comprising an effective amount of an aminoguanidine composition, generally in a pharmaceutically acceptable carrier. The invention also provides a composition comprising an aminoguanidine composition which can be formulated in a pharmaceutically acceptable carrier, in a topical application form or for oral administration. The composition finds use in alleviating symptoms associated with the disease, such as reducing size, thickness or scales of a psoriatic lesion, reducing erthema, decreasing itching and decreasing induration.

Methods and composition for treating skin proliferative diseases

The present invention relates to compositions and methods for inhibiting protein aging. Accordingly, a composition is disclosed which comprises an agent or compound capable of inhibiting the formation of advanced glycosylation end products of target proteins by reacting with the carbonyl moiety of the early glycosylation product of such target proteins formed by their initial glycosylation. Suitable agents may contain an active nitrogen-containing group, such as a hydrazine group. Particular agents comprise aminoguanidine, .alpha.-hydrazinohistidine and mixtures thereof. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated.

Compositions, including pharmaceutical compositions, for inhibiting the

The present invention relates to a method and associated agents for the inhibition and treatment of protein aging in animals by stimulating the bodies of the animals to increase their recognition and affinity for advanced glycosylation end products. Specifically, the method contemplates the administration of certain agents such as advanced glycosylation endproducts, such endproducts as are bound to the carrier, monokines that stimulate phagocytic cells to increase their activity toward advanced glycosylation endproducts, and mixtures of these materials either alone, or in conjunction with other co-stimulatory agents. Numerous diagnostic and therapeutic applications are defined, and pharmaceutical compositions are also contemplated.

Method and agents for removing advanced glycosylation endproducts

The present invention relates to compositions and methods for inhibiting protein aging. Accordingly, a composition is disclosed which comprises an agent or compound capable of inhibiting the formation of advanced glycosylation end products of target proteins by reacting with the carbonyl moiety of the early glycosylation product of such target proteins formed by their initial glycosylation. Suitable agents may contain an active nitrogen-containing group, such as a hydrazine group. Particular agents comprise aminoguanidine, .alpha.-hydrazinohistidine and mixtures thereof. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be tre

Method and agents for inhibiting protein aging

The present invention relates to compositions and methods for inhibiting protein aging. Accordingly, a composition is disclosed which comprises an agent or compound capable of inhibiting the formation of advanced glycosylation end products of target proteins by reacting with the carbonyl moiety of the early glycosylation product of such target proteins formed by their initial glycosylation. Suitable agents may contain an active nitrogen-containing group, such as a hydrazine group, and may further be at least partially derived from amino acids. Particular agents comprise aminoguanidine, .alpha.-hydrazinohistidine and lysine. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated.

A process for sulphation and phosphorylation of a protein or peptide comprising contacting said protein or peptide with sulphuric or phosphoric acid in the presence of a non-aqeuous apolar organic solvent and contacting the resultant solution with a dehydrating agent is disclosed. Non-aggregating insulin products with bioactivity may be prepared by this process.

Process for sulphation and phosphorylation of proteins and peptides

A process for sulphation and phosphorylation of a protein or peptide comprising contacting said protein or peptide with sulphuric or phosphoric acid in the presence of a non-aqueous apolar organic solvent and contacting the resultant solution with a dehydrating agent is disclosed. Non-aggregating insulin products with bioactivity may be prepared by this process.

A process and system for controlled delivery of a biologically active substance to an animal body fluid which comprises contacting fluid with a reversible complex of a conjugate (1) and a binding macromolecule (2), wherein the conjugate (1) comprises a biologically active portion which is intended to be proportionately released into a body fluid stream in response to varying concentration levels of a component of the body fluid stream, and a complexing substrate portion which conjugates with the biologically active portion and which is characterized by affinity to the binding macromolecule (2), competitivey or non-competitively with the variable component of the body fluid; thereby causing the component present in the body fluid to complex to the binding macromolecule and thus releasing the conjugate (1) therefrom into the fluid. The process and system are particularly applicable for the glucose-controlled release of insulin and other hypoglycemic agents in the treatment of diabetes.

Growing community of inventors

New York, NY, United States of America

Michael A Brownlee