University of California

The Uab Research Foundation (the University of Alabama at Birmingham)

Other

Alan M Fogelman

Mohamad Navab

Gattadahalli M Anantharamaiah

Srinivasa T Reddy

Susan Hama

Gattadahalli M Anantharmaiah

Martin Rudolf

Mohammad Navab

In various embodiments, ezetimibe-associated apoA-I mimetic peptide are provided that show improved synergistic activity between ezetimibe and the apoA-I peptide in vivo. In certain embodiments the peptide component is a transgenic 6F and the ezetimibe-associated apoA-I mimetic peptide is an Ez-T6F peptide. Methods of making the Ez-apoA-I peptides are also provided. In certain embodiments the methods involve incubating ezetimibe and an apoAI mimetic peptide (e.g., T6F) in a solution comprising ethyl acetate and acetic acid or in a solution comprising ethyl lactate and lactic acid; and drying the solution to provide a dry ezetimibe-associated apoA-I mimetic peptide.

Ezetimibe-associated ApoA-I mimetic peptides showing enhanced synergism

In certain embodiments transgenic plants (e.g., transgenic tomatoes) are provided that comprise cells that express a peptide one or more domains of which comprise the amino acid sequence of an apolipoprotein or apolipoprotein mimetic peptide where the peptide has biological activity (e.g., lowers SAA, and/or increases paroxonase activity, and/or improves HDL inflammatory index, etc.) when the plant and/or the peptide is fed to a mammal.

Modulating disease through genetic engineering of plants

This invention provides novel active agents (e.g. peptides, small organic molecules, amino acid pairs, etc.) peptides that ameliorate one or more symptoms of eye disease and/or other pathologies characterized by an inflammatory response. In certain embodiment, the peptides resemble a G* amphipathic helix of apolipoprotein J. The agents are highly stable and readily administered via an oral route or via intraocular injection.

Peptides and peptide mimetics to treat pathologies associated with eye disease

This invention provides novel peptides that ameliorate one or more symptoms of atherosclerosis. The peptides are highly stable and readily administered via an oral route. The peptides are effective to stimulate the formation and cycling of pre-beta high density lipoprotein-like particles and/or to promote lipid transport and detoxification. This invention also provides a method of tracking a peptide in a mammal. In addition, the peptides inhibit osteoporosis. When administered with a statin, the peptides enhance the activity of the statin permitting the statin to be used at significantly lower dosages and/or cause the statins to be significantly more anti-inflammatory at any given dose.

Orally administered peptides synergize statin activity

The present invention relates to the unexpected finding that vessels smaller than even the smallest arteries (i.e. arterioles) thicken, become dysfunctional and cause end organ damage to tissues as diverse as the brain and the kidney. Methods are provided to improve the structure and function of arterioles and to preserve the function of end organs such as the brain and kidney. In various embodiments the methods involve administering to a mammal in need thereof 'D' or 'L' class A amphipathic helical peptides.

Methods for improving the structure and function of arterioles

This invention pertains to the surprising discovery that salicylanilides, e.g., niclosamide and/or niclosamide analogues when orally administered in conjunction with a peptide pharmaceutical (e.g., a class A amphipathic helical peptide as described herein) significantly increases the bioavailability of that peptide. Methods of peptide delivery using such 'delivery agents' and pharmaceutical formulations are provided.

Salicylanilides enhance oral delivery of therapeutic peptides

This invention provides novel active agents (e.g. peptides, small organic molecules, amino acid pairs, etc.) peptides that ameliorate one or more symptoms of atherosclerosis and/or other pathologies characterized by an inflammatory response. In certain embodiment, the peptides resemble a G* amphipathic helix of apolipoprotein J. The agents are highly stable and readily administered via an oral route.

Peptides and peptide mimetics to treat pathologies characterized by an inflammatory response

Peptides are provided that ameliorate one or more symptoms of scleroderma. In various embodiments, the peptides range in length from about 10 to about 30 amino acids, comprise a class A amphipathic helix, and bear at least one protecting group. The peptides are highly stable and readily administered via an oral route.

Peptides for treatment of scleroderma

This invention provides novel peptides that ameliorate one or more symptoms of atherosclerosis. The peptides comprise class A amphiphathic helices, are highly stable and readily administered via an oral route. The peptides are effective to stimulate the formation and cycling of pre-beta high density lipoprotein-like particles and/or to promote lipid transport and detoxification.

This invention provides novel peptides that ameliorate one or more symptoms of atherosclerosis. The peptides are class A amphipathic helical peptides. They are highly stable and readily administered via an oral route. The peptides are effective to stimulate the formation and cycling of pre-beta high density lipoprotein-like particles and/or to promote lipid transport and detoxification. This invention also provides a method of tracking a peptide in a mammal. In addition, the peptides inhibit osteoporosis. When administered with a statin, the peptides enhance the activity of the statin permitting the statin to be used at significantly lower dosages and/or cause the statins to be significantly more anti-inflammatory at any given dose.

This invention provides novel assays for the detection of dysfunctional HDL. The assays are good diagnostics and/or prognostics for atherosclerosis or other pathologies characterized by an inflammatory response. In certain embodiments the methods involve measurements of heme-related HDL-associated proteins (e.g., haptoglobin, hemopexin, etc.), and/or measurements of the relative distribution of HDL-associated proteins between HDL and the non-lipoprotein fractions of plasma/serum, and/or measurements of the ability of pro-inflammatory HDL to consume nitric oxide, and/or measurement of the ability of HDL to inhibit LDL aggregation.

Assays to predict atherosclerosis and dysfunctional high-density lipoprotein

This invention provides novel peptides that ameliorate one or more symptoms of atherosclerosis and/or other pathologies characterized by an inflammatory response. In certain embodiment, the peptides resemble a G* amphipathic helix of apolipoprotein J. The peptides are highly stable and readily administered via an oral route.

G-type peptides to ameliorate atherosclerosis

The present invention relates to the unexpected finding that vessels smaller than even the smallest arteries (i.e. arterioles) thicken, become dysfunctional and cause end organ damage to tissues as diverse as the brain and the kidney. This invention provides a method to improve the structure and function of arterioles and preserve the function of end organs such as the brain and kidney. In certain embodiments, the methods involve administering to a human having thickened arterioles in brain, kidney or alveoli a peptide that ranges in length up to 30 amino acids, and that comprises a class A amphipathic helix, and bears at least one protecting group.

This invention provides novel peptides that ameliorate one or more symptoms of atherosclerosis. In certain embodiments, the peptides comprise an 18 amino acid class A amphipathic helix with protecting groups on the amino and the carboxyl terminus. The peptides are highly stable, readily administered via an oral route, and effective to stimulate the formation and cycling of pre-beta high density lipoprotein-like particles, and/or to promote lipid transport and detoxification. When administered with a statin, the peptides enhance the activity of the statin permitting the statin to be used at significantly lower dosages and/or cause the statins to be significantly more anti-inflammatory at any given dose.

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Beverly Hills, CA, United States of America

Alan M Fogelman