University of California

Yury Miller

Tony L Yaksh

Richard Klemke

Longhou Fang

Konstantin Stoletov

In alternative embodiments, provided are methods for increasing levels of and/or upregulating the expression of ApoA-I Binding Protein (APOA1BP, AIBP, or AI-BP) to treat, ameliorate, prevent, reverse, decrease the severity or duration of: a neuropathic pain, including an inflammation-induced neuropathic pain, a nerve or CNS inflammation, a, a post nerve injury pain, a post-surgical pain, a chemotherapeutic-induced peripheral neuropathy (CIPN) (e.g., cisplatin-induced allodynia) a neurodegeneration or neurodegenerative disease or condition, a migraine, and/or a hyperalgesia. In alternative embodiments, provided are methods comprising administering formulations and pharmaceutical compositions comprising an APOA1BP polypeptide or protein that is a human or a mammalian APOA1BP, or an AIBP1 or an AIBP2, or a recombinant, peptidomimetic or a synthetic APOA1BP, or a bioisostere of an ApoA-I Binding Protein to treat, ameliorate prevent, reverse, decrease the severity of a neuropathic pain, a TLR4-mediated allodynia and/or a hyperalgesia.

Compositions and methods for treating or ameliorating neuroinflammation, neurodegeneration, neuropathic pain, and migraine

The invention provides pharmaceutical compounds and formulations comprising nucleic acids and polypeptides for regulating (including upregulating or inhibiting) the expression of ApoA-1 Binding Protein (APOAIBP, AIBP, or AI-BP) and methods for making and using them. In alternative embodiments, APOAIBP-inhibiting pharmaceutical compositions and formulations of the invention are administered to an individual in need thereof in an amount sufficient to stimulate tissue revascularizaton, e.g., supporting or stimulating revascularization of heart tissue, e.g., after a cardiac ischemia. In alternative embodiments, pharmaceutical compositions and formulations of the invention that comprise APOAIBP nucleic acids and polypeptides or result in an increase in expression or activity of APOAIBP nucleic acids and polypeptides are administered to an individual in need thereof in an amount sufficient to treat, prevent, reverse and/or ameliorate a dyslipidemia, e.g., to treat, prevent, reverse and/or ameliorate conditions responsive to increasing cholesterol efflux from cells, including cardiovascular disease and atherosclerosis.

Methods for treating inflammatory responses or diseases caused by inflammation using ApoA-I binding protein (APOA1BP)

The invention provides genetically altered fish of the family Cyprinidae, or genus, including zebrafish () and host cells from these animals, where the fish have been genetically altered to lack or have a modified gene related to lipid metabolism, for example, an ApoE, ApoAI and/or LDL-R gene. In another aspect, the invention is directed to drug design or discovery using the animal or cell models of the invention and/or wild type zebrafish, and by administering an altered diet and/or environment to the animal of invention. The invention also provides methods for screening for a compound capable of ameliorating or preventing or reversing: atherosclerosis; hyperlipidemia; lipoprotein oxidation; the accumulation of lipid in a blood vessel wall; vascular inflammation associated with lipid accumulation in a blood vessel wall; acute atherosclerosis-associated events; heart attack; stroke.

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La Jolla, CA, United States of America

Yury Miller