This technology is a method for using osteocalcin hormone therapy to alleviate age-related muscle wasting or lung disorders while also treating associated metabolic, male reproductive, or cognitive disorders.
Unmet Need: Treatment for age-related frailty
Frailty is a natural part of the aging process, and generally refers to a collection of disorders including muscle wasting, bronchoconstriction-related lung disorders (e.g., asthma, bronchitis, COPD), metabolic disorders (e.g., diabetes, glucose intolerance, atherosclerosis, obesity), male reproductive disorders (e.g., infertility, low sperm count), and cognitive disorders (e.g. depression, memory loss). Currently, the only proven treatment for sarcopenia – age-related loss of muscle fitness and strength – is regulation of diet and exercise. Recently, it has been demonstrated that the blood circulating levels of the multifunctional, osteoblast-derived hormone osteocalcin decline with age. As such, it is possible that a decrease in osteocalcin levels may lead to frailty during aging; however, there are not currently any methods for osteocalcin hormone replacement that may alleviate age-related frailty.
The Technology: Osteocalcin hormone therapy improves muscle function
This technology is a method for treating age-related frailty and associated disorders by administering a therapeutic amount of undercarboxylated or uncarboxylated osteocalcin. Osteocalcin is a small protein comprised of 46-50 amino acid residues that is the most abundant non-collagenous protein in the mineralized bone matrix. It is an important regulator of glucose metabolism, and has been suggested as a potential treatment for diabetes. Osteocalcin also improves uptake of glucose by muscle and increases fatty acid oxidation and protein synthesis in muscle. Osteocalcin-deficient mice are prone to muscle wasting and have decreased muscle mass and function, as are mice that are deficient in osteocalcin’s receptor GPRC6A. As such, therapeutic administration of osteocalcin may help prevent or reverse age-related frailty and associated disorders.
Osteocalcin injections have been shown to improve muscle function by up to 20% in a mouse model of aging.
Applications:
- Treatment and prevention of age-related and disease-related muscle wasting
- Treatment and prevention of diabetes-related muscle atrophy
- Treatment and prevention of muscle atrophy from diseases such as muscular dystrophy, ALS, Guillian-Barre Syndrome, Dejerine–Sottas syndrome, Charcot-Marie-Tooth syndrome, multiple sclerosis
- Treatment of lung disorders involving bronchoconstriction, including asthma, bronchitis, or chronic obstructive pulmonary disease (COPD)
- Treatment of metabolic disorders including metabolic syndrome, glucose intolerance, type 1 diabetes, type 2 diabetes, atherosclerosis, or obesity
- Treatment for male reproductive disorders including male infertility, low sperm count, impaired sperm motility, impaired sperm viability, low testosterone levels, reduced libido, erectile dysfunction, underdevelopment of testes, or excess apoptosis in testes
- Treatment of cognitive disorders due to neurodegeneration including anxiety, depression, memory loss or learning difficulties
Advantages:
- There are no FDA-approved therapies for muscle wasting
- Improves muscle’s ability to metabolize glucose, synthesize proteins, and oxidize fatty acids
- Can treat disorders associated with age-related frailty, including lung disorders and metabolic, male reproductive, or cognitive disorders
Lead Inventor:
Gerard Karsenty, M.D., Ph.D.
Patent Information:
Patent Issued
Related Publications:
Wei J, Hanna T, Suda N, Karsenty G, Ducy P. “Osteocalcin promotes beta-cell proliferation during development and adulthood through Gprc6a” Diabetes. 2014 Mar; 63(3): 1021-31.
Oury F, Khrimian L, Denny CA, Gardin A, Chamouni A, Goeden N, Huang YY, Lee H, Srinivas P, Gao XB, Suyama S, Langer T, Mann JJ, Horvath TL, Bonnin A, Karsenty G. “Maternal and offspring pools of osteocalcin influence brain development and functions” Cell. 2013 Sep 26; 155(1): 228-41.
Oury F, Ferron M, Huizhen W, Confavreux C, Xu L, Lacombe J, Srinivas P, Chamouni A, Lugani F, Lejeune H, Kumar TR, Plotton I, Karsenty G. “Osteocalcin regulates murine and human fertility through a pancreas-bone-testis axis” J Clin Invest. 2013 Jun;123(6): 2421-33.
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