The University of Chicago

Arch Development Corporation

F Gary Toback

Margaret M Walsh-Reitz

Terence E Martin

John C Lieske

Stephen L Gluck

Miriana Choudhary, Legal Representative

C Thomas Powell

Thomas C Powell

Kan Agarwal

Margaret Walsh-Reitz

Terrence E Martin

A novel group of gastrokines called Gastric Antrum Mucosal Protein is characterized. A member of the group is designated AMP-18. AMP-18 genomic DNA, cDNA and the AMP-18 protein are sequenced for human, mouse and pig. The AMP-18 protein and active peptides derived from it are cellular growth factors. Surprisingly, peptides capable of inhibiting the effects of the complete protein, are also derived from the AMP-18 protein. Cytoprotection and control of mammalian gastro-intestinal tissue growth and repair (restitution) is facilitated by the use of the proteins, making the proteins candidates for therapies in inflammatory bowel disease and gastric ulcers.

Control of growth and repair of gastro-intestinal tissues by gastrokines and inhibitors

A novel group of gastrokines called Gastric Antrum Mucosal Protein is characterized. A member of the group is designated AMP-18. AMP-18 genomic DNA, cDNA and the AMP-18 protein are sequenced for human, mouse and pig. The AMP-18 protein and active peptides derived from it are cellular growth factors. Surprisingly, peptides capable of inhibiting the effects of the complete protein, are also derived from the AMP-18 protein. Cytoprotection and control of mammalian gastro-intestinal tissue growth and repair (restitution) is facilitated by the use of the proteins, making the proteins candidates for therapies in inflammatory bowel disease, mucositis, and gastric ulcers.

Methods and compositions of AMP-18 derived peptides enablingly demonstrate that AMP-18 derived peptide compositions surprisingly reduce mucositis in mammals. Methods and peptide compositions treat mucositis, delays the onset or duration of mucositis, including cancer therapy-induced mucositis are disclosed. AMP 77-97 peptide derived from human AMP-18 protein alleviates cancer therapy-induced mucositis.

Methods and compositions to treat mucositis

A novel group of gastrokines called Gastric Antrum Mucosal Protein is characterized. A member of the group is designated AMP-18. AMP-18 genomic DNA, cDNA and the AMP-18 protein are sequenced for human, mouse and pig. The AMP-18 protein and active peptides derived from it are cellular growth factors. Surprisingly, peptides capable of inhibiting the effects of the complete protein, are also derived from the AMP-18 protein. Control of mammalian gastro-intestinal tissues growth and repair is facilitated by the use of the proteins, making the proteins candidates for therapies.

Gastrokines and derived peptides including inhibitors

Novel growth peptides derived from protein factors having molecular weights of about 22 and 45 kDa stimulate mitogenic activity of epithelial, but not fibroblastic cells, in particular, kidney epithelial cells. A source of the factors is scrape-wounded kidney epithelial cells in culture. Synthetic peptides having sixteen amino acids or less, in particular a hexapeptide, YPQGNH (SEQ ID NO: 2) maintain the mitogenic activity. The peptide AQPYPQGNHEASYG (14-Ser) (SEQ ID NO: 15) is effective in reversing acute renal failure in animals. The growth-promoting characteristics of the 22 and 45 kDa proteins and the peptides are useful in treating and diagnosing patients with kidney disease. Nucleotide sequences that encode the factor are useful to develop probes to locate similar factors, to identify genetic disorders involving the factor, and to produce the factor by genetic recombinant methods. The nucleotide sequences and fragments thereof, are also useful for diagnosis and treatment of kidney disorders.

Methods for production of growth-promoting proteins and peptides for kidney epithelial cells

An autocrine crystal adhesion inhibitor called CAI is an anionic, sialic acid-containing glycoprotein secreted by kidney epithelial cells that blocks adhesion of calcium oxalate monohydrate (COM) crystals to the cell surfaces. Novel amino acid sequences are shown for the amino-acid terminus and 6 interval fragments. Persons may be classified according to risk of developing kidney stones, by measuring the amount of CAI in a biological sample. Treatment efficacy is also monitored by this method. CAI is administered in vivo to prevent nephrolithiasis. A rapid, simple assay to detect agents that inhibit adhesion of COM crystals to the surface of kidney epithelial cells is characterized.

Methods and compositions for detecting and treating kidney diseases associated with adhesion of crystals to kidney cells

Growth-promoting proteins and peptides for kidney epithelial cells

An autocrine crystal adhesion inhibitor called CAI is an anionic, sialic acid-containing glycoprotein secreted by kidney epithelial cells that blocks adhesion of calcium oxalate monohydrate (COM) crystals to the cell surface. Novel amino acid sequences are shown for the amino-acid terminus and 6 interval fragments. Persons may be classified according to risk of developing kidney stones, by measuring the amount of CAI in a biological sample. Treatment efficacy is also monitored by this method. CAI is administered in vivo to prevent nephrolithiasis. A rapid, simple assay to detect agents that inhibit adhesion of COM crystals to the surface of kidney epithelial cells is characterized.

Methods and composition for detecting and treating kidney diseases

Autocrine growth factors and isoforms of those factors have been identified, isolated, purified and manipulated. Nucleic acid segments coding for the factors, and antibodies directed to the factors are also aspects of the present invention. The effect of these growth factors on cells is to enhance their growth by increasing mitogenesis. In particular, the growth factors stimulate kidney epithelial cell growth. The growth factors differ from others previously reported in their molecular weights and other properties, for example, resistance to denaturation by dithiothreitol. Methods of preparation and use of the factors are also described. The growth factors are released from kidney epithelial cells by short exposures to a low-sodium environment. The factors have potential for treatment of kidney disease.

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Chicago, IL, United States of America

F Gary Toback