Method of Treating Neurological Conditions with Oleandrin
AssigneePhoenix Biotechnology, Inc.
InventorsOtis C. ADDINGTON, Robert A. NEWMAN
Life of this patent
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Abstract
A method of treating neurological condition in a subject by administration of a cardiac glycoside is provided. Alzheimer's disease, Huntington's disease or stroke are treated by administering a therapeutically effective amount of cardiac glycoside to a subject. The cardiac glycoside can be present in a dosage form.
Claims89
1) A method of treating a neurological condition in a subject comprising:
- administering to a subject in need thereof a composition comprising oleandrin in an effective amount to treat said neurological condition, wherein the composition provides improved treatment as compared to administration of an equivalent dose of neriifolin.
5) A method for improving the clinical status of a statistically significant number of subjects in a population of subjects having a neurological condition, the method comprising:
- administering to the population of subjects cardiac glycoside or cardiac glycoside-containing composition;
- and determining the clinical status of the subjects;
- wherein the composition provides improved clinical status as compared to administration of an equivalent dose of neriifolin.
6) A method of reducing the incidence of occurrence of a neurological condition in a population of subjects at risk thereof, the method comprising administering an effective dose of cardiac glycoside or cardiac glycoside-containing composition on a recurring basis for an extended period of time to one or more subjects in a population of subjects at risk of suffering from a neurological condition selected from Alzheimer's disease, Huntington's disease, stroke or other neurological condition, thereby reducing the incidence of the neurological condition in the population;
- wherein the composition provides enhanced reduction in the incidence of occurrence as compared to administration of an equivalent dose of neriifolin.
7) A time-delayed method of treating stroke in a subject comprising:
- within an acceptable delay period after a subject has suffered the stroke, administering an initial dose of cardiac glycoside or cardiac glycoside-containing composition according to an initial dosing regimen;
- determining the adequacy of subject's clinical response and/or therapeutic response to treatment;
- and
- if the subject's clinical response and/or therapeutic response is adequate, then continuing treatment with cardiac glycoside or cardiac glycoside-containing composition as needed until the desired clinical endpoint is achieved;
- or
- if the subject's clinical response and/or therapeutic response are inadequate at the initial dose and initial dosing regimen, then escalating or deescalating the dose until the desired clinical response and/or therapeutic response in the subject is achieved;
- wherein the composition provides improved treatment as compared to administration of an equivalent dose of neriifolin.
10) The method according to any one of the above claims, wherein cardiac glycosides is included in an extract from oleander plant mass, and the extract further comprises one or more other therapeutically effective agents obtained by extraction from oleander plant mass.
13) The method according to any one of the above claims, wherein the cardiac glycoside is oleandrin.
14) The method according to any one of the above claims, wherein, following administration thereof, oleandrin crosses the blood brain barrier and is retained in brain tissue for a period of at least 8 hours.
15) The method according to any one of the above claims wherein the neurological condition is ischemic stroke or stroke-mediated ischemic brain injury.
16) The method according to any one of the above claims wherein the subject is prescribed and administered a therapeutically effective dose of composition comprising oleandrin.
17) The method according to any one of the above claims wherein administration of the composition provides a plasma concentration of oleandrin in the subject in the range of 0.005 to 10 ng/ml.
18) The method according to any one of the above claims wherein the composition comprises 0.1 to 50 mg of oleandrin.
19) The method according to any one of the above claims wherein a subject is administered a dose of 12 to 1200 μg of oleandrin.
20) The method according to any one of the above claims, wherein the subject is administered 0.6 mg to 4.8 mg of oleandrin per day.
21) The method according to any one of the above claims wherein the subject is administered the composition comprising oleandrin according to a prescribed dosing regimen.
22) The method according to any one of the above claims wherein the composition further comprises one or more other therapeutically effective agents.
23) The method according to any one of the above claims wherein the recurring basis is daily, every other day, every second day, every third day, every fourth day, every fifth day, every sixth day, weekly, every other week, every second week, every third week, monthly, bimonthly, semi-monthly, every other month every second month, quarterly, every other quarter, trimesterly, seasonally, semi-annually and/or annually.
24) The method according to any one of the above claims wherein the extended period is one or more weeks, one or more months, one or more quarters and/or one or more years.
25) The method according to any one of the above claims wherein the effective dose is administered one or more times in a day.
26) The method according to any one of the above claims wherein the method further comprises identifying a population of subjects at risk of suffering from a neurological condition selected from Alzheimer's disease, Huntington's disease, stroke, Parkinson's disease or other neurological condition.
27) The method according to claim 27, wherein the population of subjects at risk is characterized by advancing age of the subject, familial history of the neurological condition, genetic predisposition to occurrence of neurological condition, the presence and expression of ApoE4 gene in the subject, female gender, cardiovascular disease (e.g. high blood pressure and high cholesterol levels), diabetes (especially Type 2 or adult onset forms of this disease), Down's Syndrome, head injury, low levels of formal education, smoking, excessive alcohol consumption and/or drug abuse.
28) The method according to any one of the above claims wherein the neurodegenerative disease is selected from the group consisting of Huntington's disease, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, bovine spongiform encephalopathy, multiple sclerosis, diabetic neuropathy, autism and juvenile neuronal ceroid lipofuscinosis.
29) The method according to any one of the above claims wherein oleandrin is present in a pharmaceutical formulation or composition.
30) The method according to any one of the above claims wherein oleandrin crosses the blood brain barrier (BBB) after administration to the subject.
31) The method according to any one of the above claims wherein oleandrin has a clearance rate for brain tissue of no greater than 4 L/hr.
32) The method according to any one of the above claims wherein the composition excludes neriifolin.
33) The method according to any one of the above claims wherein the composition comprises oleandrin and one or more other non-cardiac glycoside pharmacologically active components that contribute additively or synergistically to the efficacy of oleandrin.
34) The method according to any one of the above claims wherein oleandrin provides improved clinical benefit over neriifolin administered at an equivalent dose.
35) The method according to any one of the above claims, wherein oleandrin is the sole active agent present in the composition.
37) A method of treating a neurological condition in a subject comprising:
- administering to a subject in need thereof a dose of 12 to 1200 μg of oleandrin, wherein the oleandrin provides improved treatment as compared to administration of an equivalent dose of neriifolin.
41) A method for improving the clinical status of a statistically significant number of subjects in a population of subjects having a neurological condition, the method comprising:
- administering to the subjects a dose of 12 to 1200 μg of oleandrin;
- and determining the clinical status of the subjects;
- wherein the oleandrin provides improved clinical status as compared to administration of an equivalent dose of neriifolin.
42) A method of reducing the incidence of occurrence of a neurological condition in a population of subjects at risk thereof, the method comprising administering a dose of 12 to 1200 μg of oleandrin on a recurring basis for an extended period of time to one or more subjects in a population of subjects at risk of suffering from a neurological condition selected from Alzheimer's disease, Huntington's disease, stroke or other neurological condition, thereby reducing the incidence of the neurological condition in the population;
- wherein the oleandrin provides enhanced reduction in the incidence of occurrence as compared to administration of an equivalent dose of neriifolin.
43) A time-delayed method of treating stroke in a subject comprising:
- within an acceptable delay period after a subject has suffered the stroke, administering an initial dose of 12 to 1200 μg of oleandrin according to an initial dosing regimen;
- determining the adequacy of subject's clinical response and/or therapeutic response to treatment with oleandrin;
- and
- if the subject's clinical response and/or therapeutic response is adequate, then continuing treatment with oleandrin as needed until the desired clinical endpoint is achieved;
- or
- if the subject's clinical response and/or therapeutic response are inadequate at the initial dose and initial dosing regimen, then escalating or deescalating the dose until the desired clinical response and/or therapeutic response in the subject is achieved;
- wherein the oleandrin provides improved treatment as compared to administration of an equivalent dose of neriifolin.
65) A method of treating stroke in a subject comprising:
- within an acceptable delay period after the subject has suffered a stroke, administering to the subject a dose of 12 to 1200 μg of oleandrin,
- wherein the oleandrin provides improved treatment as compared to administration of an equivalent dose of neriifolin.
72) A method of treating a neurological condition in a subject comprising:
- administering to a subject in need thereof a composition comprising oleandrin in an effective amount to treat said neurological condition, wherein the subject is prescribed and administered a therapeutically effective dose of composition comprising oleandrin one or more times daily to provide a plasma concentration of oleandrin in the subject in the range of 0.005 to 10 ng/ml, and the composition provides improved treatment as compared to administration of an equivalent dose of neriifolin.
73) A method of treating a neurological condition in a subject comprising:
- administering to a subject in need thereof a therapeutically effective dose of oleandrin-containing composition sufficient to provide a plasma concentration of oleandrin in the range of 0.005 to 10 ng/ml.
74) A method for improving the clinical status of a statistically significant number of subjects in a population of subjects having a neurological condition, the method comprising:
- administering to subjects in the population a therapeutically effective dose of oleandrin-containing composition sufficient to provide a plasma concentration of oleandrin in the range of 0.005 to 10 ng/ml.
75) A method of reducing the incidence of occurrence of a neurological condition in a population of subjects at risk thereof, the method comprising administering a therapeutically effective dose of oleandrin-containing composition on a recurring basis for an extended period of time to one or more the subjects in the population, wherein the therapeutically effective dose is sufficient to provide a plasma concentration of oleandrin in the range of 0.005 to 10 ng/ml, thereby reducing the incidence of the neurological condition in the population.
77) A time-delayed method of treating stroke in a subject comprising:
- within an acceptable delay period after a subject has suffered the stroke, administering a therapeutically effective dose of oleandrin-containing composition sufficient to provide a plasma concentration of oleandrin in the range of 0.005 to 10 ng/ml.
Dependencies are inferred from the claim text.