Myricanol derivatives and uses thereof for treatment of neurodegenerative diseases
Inventors
Dickey, Chad • Jinwal, Umesh • Calcul, Laurent • Baker, Bill J. • Lebar, Matthew
Assignees
US Department of Veterans Affairs • University of South Florida St Petersburg
Publication Number
US-10358405-B2
Publication Date
2019-07-23
Expiration Date
2033-04-08
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Abstract
The subject invention pertains to myricanol derivatives, therapeutic compositions, and methods for treatment of neurodegenerative diseases, in particular, neurodegenerative diseases associated with abnormal accumulation of protein tau.
Core Innovation
The invention provides myricanol derivatives, therapeutic compositions, and methods for treating neurodegenerative diseases, specifically those associated with abnormal accumulation of protein tau. These compounds notably include derivatives such as Compound 22 and Compound 23, which have been identified as potent agents for reducing intracellular tau levels.
The background addresses the problem of intracellular aggregation of phosphorylated tau protein, which is a major pathological feature of tauopathies including Alzheimer's disease and Parkinson's disease. Existing therapeutics primarily target the prevention of tau phosphorylation or aggregation, but these tangles are less toxic than soluble tau intermediates. High levels of aberrant tau intermediates that fail to be cleared cause cognitive dysfunction. Therefore, the invention aims to solve the limited efficacy of current treatments by providing agents that degrade or destabilize tau intermediates or reduce intracellular tau levels.
Claims Coverage
The patent includes one independent claim focused on a method to reduce intracellular tau levels using a compound of formula B, specifically Compound 23.
Method of reducing intracellular tau levels
A method comprising administering to cells containing protein tau an effective amount of a compound of formula B to reduce intracellular tau levels.
Use of a specific myricanol derivative
Administration of Compound 23, a specific myricanol derivative, as the active agent for reducing tau protein levels.
Treatment of neurodegenerative diseases
Application of the method to cells in a subject needing treatment for tauopathies, including various neurodegenerative diseases associated with abnormal tau accumulation.
The independent claim covers the use of a myricanol derivative (Compound 23) for reducing intracellular tau levels, particularly targeting neurodegenerative diseases classified as tauopathies such as Alzheimer's disease, highlighting its therapeutic application in humans.
Stated Advantages
The myricanol derivatives potently reduce levels of tau proteins, addressing tau clearance and destabilization of tau intermediates.
The compounds exhibit low toxicity and do not affect cellular proteins such as GAPDH, indicating a favorable safety profile.
Documented Applications
Treatment or amelioration of neurodegenerative diseases associated with abnormal accumulation of protein tau, including Alzheimer's disease and Parkinson's disease.
Use as therapeutic agents to reduce intracellular tau levels in subjects diagnosed with tauopathies such as frontotemporal dementia, corticobasal degeneration, progressive supranuclear palsy, Pick’s disease, and other related disorders.
Potential use to alleviate symptoms arising from neurodegenerative diseases including cognitive dysfunction, impaired memory, speech dysfunction, and other neurological impairments.
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