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Abscissic acid and derivatives thereof for the treatment of diseases

Inactive Publication Date: 2010-05-06
BROYLES ROBERT H +3
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0011]An aspect of the present invention relates to a method for the treatment of a disease comprising administering a therapeutically relevant amount of abscissic acid to a subject in need thereof, wherein the disease is characterized by: an increase in iron in the subject, elevated levels of beta-globin in the subject, or the production of a dysfunctional beta-globin in the subject. The disease may be a neurological disorder, such as a neurodegenerative disease. The neurodegenerative disease may be Parkinson's Disease, Friedreich's ataxia, Huntington's Disease, Alzheimer's Disease, or amyotrophic lateral sclerosis. The disease may be a cancer, a neuromuscular disorder, atherosclerosis, diabetes, hemochromatosis, or a hemoglobinopathy. The hemoglobinopathy may be sickle cell anemia. The subject may be a mammal, such as a human. The abscissic acid may be administered to the subject intranasally, intradermally, intraarterially, intraperitoneally, intracranially, intraarticularly, intrapleurally, intratracheally, intranasally, intravitreally, intratumorally, intramuscularly, intraperitoneally, intrapericardially, orally, topically, locally, via inhalation, via injection, via infusion, via continuous infusion, via localized perfusion bathing a target cell directly, via a catheter, in a lipid composition, or by any combination of the forgoing. The abscissic acid may be administered in a pharmaceutically acceptable carrier, diluent or vehicle. The method may further comprise the administration of an additional therapeutic compound. The additional therapeutic compound may provide a therapeutic effect for the treatment of a neurological disorder, such as a neurodegenerative disease. The additional therapeutic compound may be vitamin A, a vitamin A derivative, a heteroarotinoid, or a tocopherol. The heteroarotinoid may be ShetA4 or ShetA2. The tocopherol may be gamma-tocopherol or gamma-carboxyethyl hydroxychroman (gamma-CEHC). The abscissic acid may be administered in an amount sufficient to reduce the iron concentration in the brain of the subject (e.g., to reduce the iron concentration in a cell in the brain of the subject, and / or to reduce the iron concentration in the blood of the subject). The subject may be a human. The reduction may provide a therapeutic benefit to the human. The abscissic acid may be administered in an amount sufficient to induce ferritin-H synthesis in the brain of the subject. The subject may be a human. The induction may provide a therapeutic benefit to the human.

Problems solved by technology

Although increases in iron have been associated with several diseases, synthetic chemical chelators of iron have side effects that prevent their widespread use in human medicine.
Additionally, most synthetic chelators do not penetrate the blood-brain barrier and are thus of very little clinical use (e.g., in treating neurodegenerative diseases such as Parkinson's Disease).
Several compounds may be used to induce FH expression; however, problems including lack of selectivity and / or undesirable systemic effects can result from these compounds.
However, this induction is not selective since both FH and ferritin-L (ferritin light chain, FL) are produced.
Furthermore, the amount of ferritin induced by this mechanism is unlikely to correct the problem of iron overload.
However, these cytokines cause significant unwanted systemic effects in humans and experimental animals such as inflammation, thus limiting their clinical potential.
However, high doses of retinoic acid can result in vitamin toxicity.

Method used

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  • Abscissic acid and derivatives thereof for the treatment of diseases
  • Abscissic acid and derivatives thereof for the treatment of diseases
  • Abscissic acid and derivatives thereof for the treatment of diseases

Examples

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ABA is a More Potent Inducer of FH than RTA

[0084]Ferritin H (FH) can suppress globin expression and chelate iron. The inventors have developed methods of fusing cells in vitro for the purpose of creating cross-species developmental erythroid heterokaryons. Fusing nucleated adult erythroid cells of one species with embryonic / larval erythroid cells of another species led to cross induction of developmentally-specific patterns of globin gene expression, providing evidence for developmental stage-specific trans-acting factors (Barker-Harrel et al., 1988; Broyles et al., 1989). In addition to detecting cross-activation of globin genes, cross-repression was also evident in some experiments involving heterokaryons (Broyles et al., 1994). These results led to a search for a repressor of the human adult β-globin gene, the gene mutated in sickle cell disease. The inventors noted that human K562 cells, an erythroleukemia line that expresses embryonic and fetal globins but no adult β-globin, co...

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Abstract

The present invention relates generally to the fields of molecular biology and pharmacology. More particularly, it concerns the use of abscissic acid to treat various diseases, including neurodegenerative diseases and neuromuscular diseases.

Description

[0001]This application claims the benefit of U.S. Provisional Application Ser. No. 60 / 658,803 filed Mar. 4, 2005, the entire contents and disclosure of which are specifically incorporated by reference herein without disclaimer.BACKGROUND OF THE INVENTION[0002]1. Field of the Invention[0003]The present invention relates generally to the fields of molecular biology and pharmacology. More particularly, it concerns the use of abscissic acid to treat various diseases, including neurodegenerative diseases and neuromuscular diseases.[0004]2. Description of Related Art[0005]Although increases in iron have been associated with several diseases, synthetic chemical chelators of iron have side effects that prevent their widespread use in human medicine. Additionally, most synthetic chelators do not penetrate the blood-brain barrier and are thus of very little clinical use (e.g., in treating neurodegenerative diseases such as Parkinson's Disease).[0006]Ferritin H (FH) is a protein which can chel...

Claims

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Application Information

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IPC IPC(8): A61K31/355A61K31/375A61K31/19A61K31/07A61P25/28A61P25/00A61P21/00A61P9/10A61P3/10A61P25/16A61P35/00
CPCA61K31/19A61K31/355A61K31/375A61K45/06A61K2300/00A61P21/00A61P25/00A61P25/16A61P25/28A61P35/00A61P9/10A61P3/10
Inventor BROYLES, ROBERT H.FLOYD, ROBERT A.BELEGU, VISARROTH, AUSTIN C.
Owner BROYLES ROBERT H
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