Pharmaceutical composition for treating sarcopenia including glucagon-like peptide-1 receptor agonist
Inventors
Jun, Hee Sook • Park, Eun Young • Hong, Yeon Hee
Assignees
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Publication Number
US-10751392-B2
Publication Date
2020-08-25
Expiration Date
Abstract
Provided are a pharmaceutical composition for preventing or treating muscle atrophy or sarcopenia including glucagon-like peptide-1 (GLP-1), a GLP-1 fragment, a GLP-1 secretion enhancer, a GLP-1 degradation inhibitor, a GLP-1 receptor (GLP-1R) agonist, or exendin-4, and a method of treating muscle atrophy or sarcopenia by using the pharmaceutical composition. When the pharmaceutical composition for preventing or treating muscle atrophy or sarcopenia provided in the present invention is administered to a subject having sarcopenia or muscle atrophy, reduced body weight, skeletal muscle mass, and grip strength, which are caused by sarcopenia or muscle atrophy, and expression levels of genes involved in muscle production may be restored to normal states, and therefore, the composition may be widely applied to the development of effective therapeutic agents for sarcopenia or muscle atrophy.
Core Innovation
The invention relates to a pharmaceutical composition and a method for treating muscle atrophy or sarcopenia by administering a pharmaceutically effective amount of a composition comprising a GLP-1 pathway agent. The composition is selected from glucagon-like peptide-1 (GLP-1), a GLP-1 fragment, a GLP-1 receptor (GLP-1R) agonist, a GLP-1 secretion enhancer, a GLP-1 degradation inhibitor, and exendin-4.
The disclosed core focuses on using exendin-4 as a GLP-1R agonist for sarcopenia, including effects reported beyond diabetes use. In dexamethasone-induced muscle atrophy/sarcopenia mouse models, GLP-1 pathway agent treatment is described as increasing body weight, skeletal muscle mass, and grip strength, while decreasing muscle protein-destroying genes such as myostatin, atrogin-1, and MuRF1.
The documented effects also include increased expression of muscle protein-producing genes such as MyoD and myogenin. The disclosure further states that restorative effects are supported for GLP-1 fragment GLP-1(32-36)amide and for the GLP-1 degradation inhibitor sitagliptin (a DPP-4 inhibitor), including similar improvements and gene-expression changes.
Claims Coverage
The document contains two independent claims (clm-00001 and clm-00009). The independent claim set covers treating muscle atrophy or sarcopenia with GLP-1 pathway agents, with one independent claim defining a general administration framework and the other specifying intraperitoneal administration; both include the core requirement of a pharmaceutically effective amount to a subject with muscle atrophy or sarcopenia.
GLP-1 pathway agent composition for treating muscle atrophy or sarcopenia
Administering a pharmaceutically effective amount of a pharmaceutical composition comprising any one selected from glucagon-like peptide-1 (GLP-1), a GLP-1 fragment, a GLP-1 receptor (GLP-1R) agonist, a GLP-1 secretion enhancer, a GLP-1 degradation inhibitor, and exendin-4 to a subject having muscle atrophy or sarcopenia.
Intraperitoneal administration of GLP-1 pathway agent composition
Administering intraperitoneally a pharmaceutically effective amount of a pharmaceutical composition comprising any one selected from glucagon-like peptide-1 (GLP-1), a GLP-1 fragment, a GLP-1 receptor (GLP-1R) agonist, a GLP-1 secretion enhancer, a GLP-1 degradation inhibitor, and exendin-4 to a subject having muscle atrophy or sarcopenia.
Across the independent claims, the inventive coverage centers on treating muscle atrophy or sarcopenia by administering a pharmaceutically effective amount of a composition containing a GLP-1 pathway agent, with intraperitoneal administration specifically recited in the second independent claim.
Stated Advantages
Increasing body weight.
Increasing skeletal muscle mass.
Increasing grip strength.
Inhibiting expression of muscle protein-destroying genes (myostatin, atrogin-1, MuRF1).
Increasing expression of muscle protein-producing genes (MyoD, myogenin).
Documented Applications
Treating muscle atrophy or sarcopenia using GLP-1 pathway agents, with restorative effects described in dexamethasone-induced sarcopenia mouse models.
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