Pharmaceutical combination for use in age- related and/or degenerative diseases
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Publication Number
US-12090124-B2
Publication Date
2024-09-17
Expiration Date
Abstract
The present invention relates to a pharmaceutical combination for use in the treatment, prevention and/or stabilization of age-related diseases and/or degenerative diseases. In particular, said pharmaceutical combination comprises a biguanide and an acetylcholinesterase inhibitor and/or an N-oxide, a hydrate, a pharmaceutically acceptable salt or solvate thereof. The invention is further also directed to the use of said pharmaceutical combination for prevention, stabilization and/or reduction of age-related complaints and/or degenerative complaints; and for improving a measure of life span and/or health span.
Core Innovation
The invention describes a pharmaceutical combination for treating, preventing, or stabilizing age-related and degenerative diseases, particularly neuro-musculoskeletal disease. The pharmaceutical combination includes metformin together with an acetylcholinesterase inhibitor, and the acetylcholinesterase inhibitor is selected from galantamine, donepezil, rivastigmine, and memantine.
The problem addressed is the onset and progression of age-related and degenerative conditions associated with neuro-musculoskeletal disease, including sarcopenia and frailty. The objectives described include delaying onset, reducing symptoms, and improving life span and/or health span. The approach is framed around potentiation and/or synergistic effects between metformin and the selected acetylcholinesterase inhibitor when used in subtherapeutic doses.
The document provides experimental evidence intended to support the potentiating or synergistic effects, including C. elegans lifespan/healthspan assays and gst-4 transcription assays, and an OPA1 muscle-specific knockout mouse model. Reported readouts include inflammatory markers, glucose homeostasis, immunosenescence, locomotion-based healthy days, metabolic and physical performance measures, and partial preservation of muscle mass and innervation. The document also outlines exploratory human proof-of-concept studies in sarcopenic obesity and sarcopenic patients undergoing total hip arthroplasty.
Claims Coverage
The partial content provides two independent claims. Both claims cover administering a pharmaceutical combination of metformin together with an acetylcholinesterase inhibitor selected from galantamine, donepezil, rivastigmine, and memantine, for neuromusculoskeletal disease indications, including improvement of life span and/or health span.
Treating or stabilizing neuromusculoskeletal disease with metformin plus an acetylcholinesterase inhibitor
Administering to a subject in need a pharmaceutical combination comprising metformin and an acetylcholinesterase inhibitor selected from galantamine, donepezil, rivastigmine, and memantine, for treating or stabilizing a neuromusculoskeletal disease.
Improving life span and/or health span for neuromusculoskeletal disease by reducing symptom severity
Administering to a subject suffering from a neuromusculoskeletal disease a pharmaceutical combination comprising metformin and an acetylcholinesterase inhibitor selected from galantamine, donepezil, rivastigmine, and memantine, wherein the improved measure of life span and/or health span is lessening or reduction in the severity of at least one clinical symptom associated with the neuromusculoskeletal disease.
Across the independent claims, the core coverage is use of a metformin–acetylcholinesterase inhibitor pharmaceutical combination for neuromusculoskeletal disease treatment or stabilization and for improving life span and/or health span defined by reduced severity of clinical symptoms.
Stated Advantages
Treating or stabilizing a neuromusculoskeletal disease.
Improving a measure of life span and/or health span by lessening or reducing the severity of at least one clinical symptom associated with the neuromusculoskeletal disease.
Documented Applications
Treating or stabilizing neuromusculoskeletal disease, including sarcopenia and frailty.
Improving life span and/or health span in a subject suffering from a neuromusculoskeletal disease, including by reducing clinical symptom severity.
Exploratory human proof-of-concept studies in sarcopenic obesity.
Exploratory human proof-of-concept in sarcopenic patients undergoing total hip arthroplasty.
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