Clomipramine for the treatment of Alzheimer's Disease
Inventors
SHARMA, Pushkar • CHAUHAN, Monika
Assignees
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Publication Number
US-11957692-B2
Publication Date
2024-04-16
Expiration Date
Abstract
The present disclosure provides methods for treating Alzheimer's disease (AD) comprising administering clomipramine or a pharmaceutically acceptable salt thereof. The administration of clomipramine increases the levels of TAp73 and decreases the levels of proliferating cell nuclear antigen (PCNA) and cleaved caspase-3 in the AD patients. The methods of the present disclosure reduce the neurodegeneration and improve the cognitive and functional decline in AD patients.
Core Innovation
The invention describes administering clomipramine, or a pharmaceutically acceptable salt thereof, to a patient to treat Alzheimer's disease and mild cognitive impairment (MCI). Administration inhibits cell cycle related neuronal apoptosis (CRNA) in the patient by about 20-90% as measured by a decrease in levels of proliferating cell nuclear antigen (PCNA) compared to levels of PCNA prior to administration of clomipramine.
The invention further provides that clomipramine can reduce neurodegeneration in a patient suffering from Alzheimer's disease or at a risk of developing Alzheimer's disease. Mechanistic aspects described include increasing TAp73 levels while reducing CRNA-associated markers, including decreasing PCNA and cleaved caspase-3, and linking these changes to Itch/TAp73 ubiquitin-proteasome degradation.
The described framework links the CRNA inhibition endpoint to cognitive and functional improvement across stages including pre-clinical stage AD, MCI, and CDR-SOB ranges.
Claims Coverage
The claim coverage identifies three independent claims. The inventive concept is consistently expressed as administering clomipramine or a pharmaceutically acceptable salt thereof and inhibiting cell cycle related neuronal apoptosis (CRNA) by decreasing proliferating cell nuclear antigen (PCNA) by about 20-90% compared to pre-administration levels.
Treating Alzheimer's disease by inhibiting CRNA via PCNA decrease
A method for treating Alzheimer's disease in a patient in need thereof, comprising administering clomipramine or a pharmaceutically acceptable salt thereof, wherein administration inhibits cell cycle related neuronal apoptosis (CRNA) by about 20-90% as measured by a decrease in levels of proliferating cell nuclear antigen (PCNA) compared to levels prior to administration.
Reducing neurodegeneration in Alzheimer's disease or at risk by inhibiting CRNA via PCNA decrease
A method of reducing neurodegeneration in a patient suffering from Alzheimer's disease or at a risk of developing Alzheimer's disease, comprising administering clomipramine or a pharmaceutically acceptable salt thereof, wherein administration inhibits cell cycle related neuronal apoptosis (CRNA) by about 20-90% as measured by a decrease in levels of proliferating cell nuclear antigen (PCNA) compared to levels prior to administration.
Treating MCI by inhibiting CRNA via PCNA decrease
A method for treating a mild cognitive impairment (MCI) in a patient, comprising administering clomipramine or a pharmaceutically acceptable salt thereof, wherein administration inhibits cell cycle related neuronal apoptosis (CRNA) by about 20-90% as measured by a decrease in levels of proliferating cell nuclear antigen (PCNA) compared to levels prior to administration.
Across the identified independent claims, the claim coverage is anchored to administering clomipramine and inhibiting CRNA by decreasing PCNA levels by about 20-90% versus pre-administration levels.
Stated Advantages
Inhibits cell cycle related neuronal apoptosis (CRNA) by about 20-90% as measured by a decrease in PCNA levels compared to levels of PCNA prior to administration.
Improves short-term and long-term memory in the patient.
Provides functional outcome improvements described as limited functional side effects.
Documented Applications
Treating Alzheimer's disease in a patient in need thereof, including across stages such as pre-clinical stage AD and MCI/CDR-SOB ranges.
Reducing neurodegeneration in a patient suffering from Alzheimer's disease or at a risk of developing Alzheimer's disease.
Treating mild cognitive impairment (MCI) in a patient.
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