Method of treating neurological conditions with oleandrin
Inventors
ADDINGTON, Otis C. • Newman, Robert A.
Assignees
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Publication Number
US-10383886-B2
Publication Date
2019-08-20
Expiration Date
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, and optionally triterpene(s), to a subject. The cardiac glycoside can be present in a dosage form.
Core Innovation
The invention relates to treating neurological conditions in a subject by administering a neuroprotective composition that comprises oleandrin and at least one triterpene together present in an effective amount. The at least one triterpene is selected from oleanolic acid, ursolic acid, and betulinic acid, and is present in free acid form, salt form, derivative form, prodrug form, or a combination thereof.
The invention further provides that the neurological condition is treated using combinations in which oleandrin and the selected triterpene(s) are present in effective amounts, including defined molar ratios between oleandrin and the at least one triterpene. For stroke, the neuroprotective composition is administered within an acceptable delay period after a subject has suffered the stroke.
The disclosed rationale is directed to neuroprotection associated with Na,K-ATPase dysregulation and optionally HIF-1α, and to blood-brain barrier penetration and brain residence time. The patent also describes composition efficacy using brain-slice oxygen-glucose deprivation and cell-based assays assessing APP/Aβ degeneration and Huntington’s cortico-striatal co-culture outcomes.
Claims Coverage
The provided partial content includes two independent claims. Across these claims, the main inventive features are neuroprotective administration of oleandrin together with specified triterpenes in allowed chemical forms, and, for stroke, administration within an acceptable delay period after stroke onset.
Oleandrin and specified triterpene neuroprotective composition for treating neurological condition
Administering to a subject in need thereof a neuroprotective composition comprising oleandrin and at least one triterpene together present in an effective amount to treat the neurological condition, wherein the at least one triterpene is selected from oleanolic acid, ursolic acid, and betulinic acid, and wherein the at least one triterpene is present in free acid form, salt form, derivative form, prodrug form or a combination thereof.
Time-delayed stroke treatment with oleandrin and specified triterpene neuroprotective composition
Within an acceptable delay period after a subject has suffered the stroke, administering a neuroprotective composition comprising oleandrin and at least one triterpene together present in an amount sufficient to treat the stroke, wherein the at least one triterpene is selected from oleanolic acid, ursolic acid, and betulinic acid, and wherein the at least one triterpene is present in free acid form, salt form, derivative form, prodrug form or a combination thereof.
Overall, the claim coverage centers on administering oleandrin combined with one or more of oleanolic acid, ursolic acid, and/or betulinic acid as a neuroprotective composition, with permitted chemical forms of the triterpenes. The stroke-related independent claim additionally requires administration within an acceptable delay period after stroke onset.
Stated Advantages
Neuroprotective effect for treating neurological conditions, including Alzheimer’s disease, Huntington’s disease, and ischemic stroke.
Rationale based on Na,K-ATPase dysregulation and optional HIF-1α, and on blood-brain barrier penetration and brain residence time.
Documented in vitro efficacy signals using brain-slice oxygen-glucose deprivation, APP/Aβ degeneration, and Huntington’s cortico-striatal co-culture assays.
Documented Applications
Treating neurological conditions in a subject, including Alzheimer’s disease and Huntington’s disease, using a neuroprotective composition comprising oleandrin and specified triterpenes.
Time-delayed treatment of stroke in a subject using a neuroprotective composition comprising oleandrin and specified triterpenes within an acceptable delay period after stroke.
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