Methods and compositions for stimulating neurogenesis and inhibiting neuronal degeneration using isothiazolopyrimidinones
Inventors
Assignees
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Publication Number
US-9096613-B2
Publication Date
2015-08-04
Expiration Date
Abstract
The present invention provides methods and compositions comprising compounds useful for stimulating neurogenesis. The methods and compositions comprising compounds are also useful for inhibiting neuronal degeneration. Thus, the present invention can be used in the treatment of diseases and conditions characterized by neuronal loss and reduced neurogenesis including Alzheimer's disease, stroke, traumatic brain injury, traumatic nerve injury, and depression. This invention is useful for research products including single agents or mixtures of agents to promote, proliferate, differentiate, or maintain neurons from stem or progenitor cells.
Core Innovation
The invention relates to isothiazolopyrimidinone compounds and a method for stimulating neurogenesis and/or inhibiting neuronal degeneration in a mammal by administering a pharmaceutical composition. The pharmaceutical composition comprises a compound selected from the group described in the patent and a pharmaceutically acceptable excipient or carrier, and may include pharmaceutically acceptable salts, hydrates, or solvates thereof.
The disclosed subject matter is directed to therapeutic use in conditions involving neuronal loss and impaired neuronal function. The use is directed, in dependent forms, to a human patient and to a patient having a condition selected from neurodegenerative disease, brain injury, nerve injury, psychiatric disorders, or aging.
The document also describes pharmaceutical formulation and administration strategies, including kit formats and sustained or controlled release approaches such as slow-release depots and implants, polymer matrices, and microparticles/microcapsules. The therapeutic utility is described in connection with neurodegenerative and neuropsychiatric conditions and aging, supported by in vitro neurogenesis assays and neuroprotection-related tests using described models and assays [procedural detail omitted for safety].
Claims Coverage
The patent includes one independent method claim, with dependent claims narrowing the mammal to a human and further specifying condition-based use in neuronal loss related disorders.
Method for stimulating neurogenesis and/or inhibiting neuronal degeneration in a mammal
Administering a pharmaceutical composition in an amount effective to stimulate neurogenesis and/or inhibit neuronal degeneration in the mammal, wherein the pharmaceutical composition comprises a compound selected from the described isothiazolopyrimidinone compounds and a pharmaceutically acceptable excipient or carrier.
Human patient limitation
The method is carried out with the mammal being a human.
Condition-selected human use
The method is applied to a human patient having a condition selected from neurodegenerative disease, brain injury, nerve injury, psychiatric disorders, or aging.
Overall, the claim coverage centers on administration of an effective pharmaceutical composition comprising isothiazolopyrimidinone compounds to stimulate neurogenesis and/or inhibit neuronal degeneration, with narrowing to human patients and specified condition categories.
Stated Advantages
Stimulating neurogenesis.
Inhibiting neuronal degeneration.
Neurogenesis promotion and neuroprotection supported by in vitro/ex vivo biological tests described in the document.
Documented Applications
Therapeutic use for Alzheimer’s disease.
Therapeutic use for stroke.
Therapeutic use for traumatic brain injury.
Therapeutic use for traumatic nerve injury.
Therapeutic use for depression.
Therapeutic use for neurodegenerative disease.
Therapeutic use for brain injury.
Therapeutic use for nerve injury.
Therapeutic use for psychiatric disorders.
Therapeutic use for aging.
In vitro neurogenesis promotion and neuroprotection testing using described assays and models, including assays connected to neuronal progenitor cells and neurotoxicity/neuroprotection endpoints [procedural detail omitted for safety].
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