(3aR)-1,3a,8-trimethyl-1,2,3,3a,8,8ahexahydropyrrolo[2,3-b]indol-5-yl phenylcarbamate and methods of treating or preventing neurodegeneration
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Assignees
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Publication Number
US-12144798-B2
Publication Date
2024-11-19
Expiration Date
Abstract
The invention includes an amount of (3aR)-1,3a,8-trimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-5-yl phenylcarbamate for administering to a subject and also a method of preventing or treating neurotoxicity or neurodegenerative processes in a subject in need thereof using the amount thereof.
Core Innovation
The invention relates to (3aR)-1,3a,8-trimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-5-yl phenylcarbamate, described as Compound (1) and Posiphen, for preventing or treating neurodegenerative/neurotoxic processes in a human patient. The disclosed rationale centers on neurotoxic fibrillar protein misfolding/aggregation pathways involving APP/amyloid-β, tau, alpha-synuclein, prions, SOD, and HTT.
The invention further proposes a shared translational regulation mechanism that involves IRP1/IRE elements and 5′UTR control, linking translational regulation to neurotoxic aggregating protein production. It is stated that Compound (1) inhibits neurotoxic aggregating protein production, including inhibition of APP synthesis and translation of other proteins implicated in neurotoxic processes.
The patent frames the approach with pharmacokinetic/pharmacodynamic exposure concepts, including target ranges for plasma and brain levels and reductions in cerebrospinal fluid biomarkers. It also identifies metabolites (Compounds (2)-(4)) contributing to exposure, alongside pharmacodynamic biomarker reductions involving sAPPα, sAPPβ, Tau, and pTau.
Claims Coverage
The partial content provides two independent claims. The claim set centers on once-a-day administration of posiphen (or pharmaceutically acceptable salt) to ameliorate Alzheimer’s Disease, with the core inventive features including specified daily dose ranges, pharmaceutically acceptable excipients, and inhibition of neurotoxic aggregating protein production.
Once-a-day posiphen dosing with pharmaceutically acceptable excipients for ameliorating Alzheimer’s Disease
Administering a pharmaceutical composition comprising posiphen or a pharmaceutically acceptable salt thereof in an amount from about 0.1 mg/day to about 30 mg/day together with one or more pharmaceutically acceptable excipients on a once-a-day basis to a human patient suffering from Alzheimer's Disease.
Inhibiting neurotoxic aggregating protein production as a result of once-a-day posiphen dosing
Administering a pharmaceutical composition comprising from about 7.5 mg to less than about 20 mg of posiphen or a pharmaceutically acceptable salt together with one or more pharmaceutically acceptable excipients on a once-a-day basis such that the production of neurotoxic aggregating protein in the human patient is inhibited.
Across the independent claims shown, the inventive coverage is directed to ameliorating Alzheimer’s Disease via once-daily administration of posiphen (or pharmaceutically acceptable salts) within specified daily dose ranges formulated with pharmaceutically acceptable excipients, where the therapeutic outcome is tied to inhibiting neurotoxic aggregating protein production.
Stated Advantages
Ameliorates Alzheimer’s Disease in a human patient.
Inhibits production of neurotoxic aggregating protein in the human patient.
Documented Applications
Methods for preventing or treating neurodegenerative/neurotoxic processes, including Alzheimer’s Disease and dementia/neurodegenerative conditions.
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