Hormone therapy for age-related frailty and muscle degeneration

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 and correlate with increased frailty, suggesting that osteocalcin replacement therapy may be used to alleviate age-related frailty.

The Technology: Osteocalcin hormone therapy for improving muscle function

This technology is a method for treating age-related frailty and associated disorders by administering a pharmaceutical composition of undercarboxylated or uncarboxylated osteocalcin delivered via vehicle carrier. This technology is designed to target frailty symptoms in patients over the age of 55 years by inhibiting the expression or activity of the osteotesticular protein tyrosine phosphatase (OST-PTP) signaling pathway, which regulates bone maintenance through insulin. This technology also comprises alternative small-molecule approaches to block OST-PTP pathway activity. This technology has been tested in mouse models, where injections have been shown to improve muscle function by up to 20%.

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:

• Therapeutic for muscle wasting, as there are currently no FDA-approved therapies
• Improves muscles’ 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 (US 11,191,811)

Related Publications:

• Mera P, Laue K, Wei J, Berger JM, Karsenty G. “Osteocalcin is necessary and sufficient to maintain muscle mass in older mice” Mol Metab. 2016 Jul 16;5(10):1042-1047.

• Mera P, Laue K, Ferron M, Confavreux C, Wei J, Galán-Díez M, Lacampagne A, Mitchell SJ, Mattison JA, Chen Y, Bacchetta J, Szulc P, Kitsis RN, de Cabo R, Friedman RA, Torsitano C, McGraw TE, Puchowicz M, Kurland I, Karsenty G. “Osteocalcin Signaling in Myofibers Is Necessary and Sufficient for Optimum Adaptation to Exercise” Cell Metab. 2016 Jun 14;23(6):1078-1092.

• 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. 2015 May;125(5):2180.

• 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.

Tech Ventures Reference:

• IR CU15011, CU12033, CU15010

• Licensing Contact: Jerry Kokoshka