Methods for inhibiting muscle atrophy
Inventors
Adams, Christopher M. • Kunkel, Steven D. • Welsh, Michael
Assignees
University of Iowa Research Foundation UIRF • US Department of Veterans Affairs
Publication Number
US-11090313-B2
Publication Date
2021-08-17
Expiration Date
2031-05-19
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Abstract
The invention provides a method for (a) increasing skeletal muscle mass; (b) reducing skeletal muscle atrophy; (c) increasing muscular strength; (d) promoting muscle growth; (e) decreasing muscle wasting; or (f) increasing strength per unit of muscle mass in an animal identified or having been identified to be in need of one or more of (a)-(f), the method comprising administering to the animal an effective amount of a compound of formula: or a stereoisomer, solvate, or pharmaceutically acceptable salt thereof, thereby accomplishing one or more of (a)-(f).
Core Innovation
The invention provides methods for increasing skeletal muscle mass, reducing skeletal muscle atrophy, increasing muscular strength, promoting muscle growth, decreasing muscle wasting, or increasing strength per unit of muscle mass in an animal identified or having been identified to be in need of one or more of these effects. This is accomplished by administering to the animal an effective amount of certain compounds, including tacrine and analogs, naringenin and analogs, allantoin and analogs, conessine and analogs, tomatidine and analogs, ungerine/hippeastrine and analogs, and betulinic acid and analogs, or mixtures thereof.
The problem addressed is that skeletal muscle atrophy is common in aging, starvation, and many severe human illnesses including cancer, chronic renal failure, and chronic respiratory disease, among others. These conditions lead to muscle weakness, increased risk of falls and fractures, respiratory infections, and loss of independence in millions of individuals. Despite advances in the understanding of muscle atrophy pathogenesis, effective medical therapies to prevent or reverse skeletal muscle atrophy in human patients do not exist, creating an unmet need for potent, efficacious, and selective modulators of muscle growth that are effective in treating muscle atrophy-associated diseases.
Claims Coverage
The patent contains one independent claim focusing on a method for achieving one or more beneficial effects on skeletal muscle in an animal by administering specific compounds.
Method for enhancing skeletal muscle properties using specific compounds
A method for increasing skeletal muscle mass, reducing skeletal muscle atrophy, increasing muscular strength, promoting muscle growth, decreasing muscle wasting, or increasing strength per unit muscle mass in an animal by administering an effective amount of a compound or its stereoisomers, solvates, or pharmaceutically acceptable salts.
Administration of compounds at therapeutically effective doses
Methods involving administration to the animal of greater than 75 mg, 100 mg, 150 mg, and up to 2000 mg per day or dosage levels of 0.5 to 250 mg/kg per day, with various specific ranges detailed.
Use of specific animal subjects for treatment
The method applies to animals including non-human primates, domesticated fish, crustaceans, mollusks, poultry, dogs, cats, guinea pigs, livestock, and humans.
The claim covers methods of administering specified compounds at various dosages to a variety of animal subjects for improving muscle mass, strength, and health, with flexibility in dose and species treated.
Stated Advantages
The disclosed compounds effectively inhibit muscle atrophy and promote skeletal muscle hypertrophy and strength.
The compounds enhance skeletal muscle IGF-I expression and insulin/IGF-I signaling.
They reduce adiposity and improve metabolic parameters including lowering fasting blood glucose and plasma lipid levels.
The compounds increase energy expenditure, increase brown fat, and improve the ratio of skeletal muscle to fat, contributing to overall metabolic health.
Documented Applications
Treatment, prevention, and reversal of muscle atrophy associated with aging, starvation, muscle disuse, neurological diseases, chronic illnesses, drug-induced muscle diseases, genetic and autoimmune muscle diseases, surgical immobilization, burns, sepsis, and spaceflight.
Methods for promoting muscle health, promoting normal muscle function, and promoting healthy aging muscles in animals including humans.
Treatment or prevention of metabolic disorders such as obesity, pre-diabetes, diabetes, fatty liver disease, and hyperlipidemia through modulation of muscle mass and metabolism.
Use as pharmacological tools for in vitro and in vivo testing of muscle atrophy inhibitors.
Identification methods for compounds that regulate muscle atrophy-associated mRNAs (muscle atrophy signatures) to inhibit muscle atrophy.
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