Compositions and methods for treating neurodegenerative diseases
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Assignees
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Publication Number
US-11319306-B2
Publication Date
2022-05-03
Expiration Date
Abstract
Compounds, and compositions, methods, and uses thereof, are described herein for treating neurodegenerative diseases and disorders. In particular, vasopressin receptor modulators, and compositions, methods and uses thereof, are described herein for treating neuropsychiatric aspects of neurodegenerative diseases such as Huntington's Disease, Parkinson's Disease, and Alzheimer's Disease.
Core Innovation
The invention relates to a method for treating Huntington’s Disease, Parkinson’s Disease, or Alzheimer’s Disease in a host animal by administering a composition comprising one or more compounds selected from the listed formulae and pharmaceutically acceptable salts thereof. The compounds are presented with defined structural variables, example embodiments, and named compound examples.
The disclosure emphasizes vasopressin signaling and V1a-selective antagonism at the vasopressin receptor (AVPR1A), including competitive binding and functional inhibition of vasopressin receptor activity. It reports inhibition of vasopressin-mediated phosphatidylinositol turnover and pharmacological differentiation versus V1b and V2.
The disclosed approach targets neuropsychiatric aspects associated with neurodegenerative disease, including aggressive, irritability, and anger-like responses in Huntington’s Disease. The content also describes evidence from neuropsychiatric and neuroimaging-related models, including Huntington’s Disease brain V1a mRNA equivalence to control and fMRI-based models in which vasopressin antagonists reduce BOLD signals associated with excessive vasopressin signaling.
Claims Coverage
The independent claim is directed to treating Huntington’s Disease, Parkinson’s Disease, or Alzheimer’s Disease in a host animal by administering a composition comprising one or more compounds selected from the disclosed formulae, including pharmaceutically acceptable salts. The claim coverage centers on the disease-treatment method and the compound-selection framework, with dependent claims narrowing to neuropsychiatric symptoms.
Treatment of neurodegenerative disease by administering defined vasopressin receptor antagonist compounds
A method for treating Huntington’s Disease, Parkinson’s Disease, or Alzheimer’s Disease in a host animal by administering a composition comprising one or more compounds selected from the listed formulae and pharmaceutically acceptable salts thereof.
Neuropsychiatric symptom treatment in Huntington’s Disease
A method for treating one or more neuropsychiatric symptoms of Huntington’s Disease by administering the composition of the independent claim.
Aggression, irritability, and anger symptom coverage
A method in which the neuropsychiatric symptoms include aggression, irritability, or anger, or any combination thereof, in the Huntington’s Disease context.
Neuropsychiatric symptom treatment in Parkinson’s Disease
A method for treating one or more neuropsychiatric symptoms of Parkinson’s Disease by administering the composition of the independent claim.
Neuropsychiatric symptom treatment in Alzheimer’s Disease
A method for treating one or more neuropsychiatric symptoms of Alzheimer’s Disease by administering the composition of the independent claim.
Overall, the claims coverage centers on administering compositions containing compounds defined by the listed formulae and pharmaceutically acceptable salts to treat Huntington’s Disease, Parkinson’s Disease, or Alzheimer’s Disease, with dependent refinements specifying neuropsychiatric symptom treatment, including aggression, irritability, and anger, in each stated disease.
Stated Advantages
Reduces BOLD signals associated with excessive vasopressin signaling and aggressive, irritability, and anger-like responses in the described fMRI-based models.
Demonstrates V1a-selective vasopressin receptor inhibition characterized by competitive binding and functional V1a antagonism with inhibition of vasopressin-mediated phosphatidylinositol turnover.
Shows pharmacological differentiation versus V1b and V2.
Includes pharmacokinetics and CNS penetration/selectivity data.
Documented Applications
Treatment in a host animal of Huntington’s Disease, Parkinson’s Disease, or Alzheimer’s Disease using a composition comprising one or more compounds selected from the disclosed formulae, including pharmaceutically acceptable salts.
Treatment of neuropsychiatric symptoms of Huntington’s Disease, including aggression, irritability, and/or anger, or combinations thereof.
Treatment of neuropsychiatric symptoms of Parkinson’s Disease.
Treatment of neuropsychiatric symptoms of Alzheimer’s Disease.
Neuroimaging application in fMRI-based models in which vasopressin antagonists reduce BOLD signals associated with excessive vasopressin signaling and aggressive, irritability, and anger-like responses.
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