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Compositions and methods for preventing or treating muscle conditions

A composition, a muscle technique, a composition for preventing or treating muscle disorders, a muscle disorder in a subject, a kit for increasing muscle strength and/or increasing muscle mass, a pharmaceutical composition, promoting muscle regeneration, promoting Areas of muscle regeneration and/or increased muscle mass, addressing issues such as poor functional recovery

Pending Publication Date: 2020-05-29
THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Unfortunately, many of those with severe CTS have poor functional recovery even after the nerve is released

Method used

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  • Compositions and methods for preventing or treating muscle conditions
  • Compositions and methods for preventing or treating muscle conditions
  • Compositions and methods for preventing or treating muscle conditions

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0491] Example 1: Acute prostaglandin E2 delivery enhances skeletal muscle regeneration and strength in aged mice.

[0492] This example demonstrates that muscle stem cell function requires PGE2 signaling during regeneration.

[0493] Older adults suffer from progressive skeletal muscle wasting and regenerative failure, which reduces mobility and quality of life. Crucial for muscle regeneration are adult muscle stem cells (MuSC), which reside throughout their life in a niche within muscle tissue, remain responsive to injury and repair skeletal muscle. During aging, the proportion of functional MuSCs decreased significantly, hindering muscle regeneration. To date, there are no therapeutics targeting MuSCs in clinical use to combat this decline in regeneration. Here, we identify a natural immunomodulator, prostaglandin E2 (PGE2), as a potent modulator of MuSC function essential for muscle regeneration. We found that the PGE2 receptor EP4 is essential for MuSC proliferation ...

Embodiment 2

[0543] Example 2: Muscular strength increases after prostaglandin E2 (PGE2) injection.

[0544] This example shows that the specific twitch force of the gastrocnemius muscle is increased in aged mice injected with PGE2. Aged mice (18 months old) were run daily on a treadmill to fatigue for 10 days. Treadmill running was performed using Exer3 / 6 (Columbus Instruments). Mice started running on a treadmill with a 20-degree downhill slope at a speed of 10 m / min. After 3 min, the speed was increased by 1 m / min to reach a final speed of 20 m / min. Fatigue was defined as the inability of the animal to remain on the treadmill despite electrical stimulation. Two hours after each treadmill run, both gastrocnemius muscles of each mouse were injected with PBS (control group) or 3 nM PGE2 (experimental group). Four weeks after the last treadmill run, force measurements were performed using a 300C-LR force transducer (Aurora Scientific) with a single 0.1 ms pulse at a predetermined supr...

Embodiment 3

[0547] Example 3: Prostaglandin E2 is essential for efficient skeletal muscle stem cell function, thereby enhancing regeneration and force quantity .

[0548] Skeletal muscle harbors quiescent muscle-specific stem cells (MuSCs) capable of tissue regeneration throughout life. Muscle injury drives a complex inflammatory response involving multiple cell types, cytokines, and growth factors, including prostaglandins. Here we show that prostaglandin E2 (PGE2) directly targets MuSCs via the EP4 receptor, leading to MuSC expansion. Acute treatment with PGE2 was sufficient to robustly enhance muscle regeneration by endogenous or transplanted MuSCs. Specific genetic ablation of the EP4 receptor in MuSCs leading to loss of PGE2 signaling impairs regeneration, resulting in reduced muscle strength. Inhibition of PGE2 production by NSAID administration just after injury likewise hinders regeneration and impairs muscle strength. Mechanistically, PGE2EP4 interaction causes MuSC expans...

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Abstract

Provided herein are compositions for preventing or treating muscle conditions such as muscle damage, injury, or atrophy. In some embodiments, the compositions comprise a prostaglandin E2 (PGE2) compound and a myotoxin. In some embodiments, the muscle damage, injury, or atrophy is the result of a nerve injury, a surgical procedure, or a traumatic injury. Methods of promoting muscle regeneration andmethods of increasing muscle mass are also provided herein.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to US Provisional Application No. 62 / 517,758, filed June 9, 2017, the disclosure of which is hereby incorporated by reference in its entirety for all purposes. [0003] Statement Regarding Invention Rights Acquired Under Federally Sponsored Research and Development [0004] This invention was made with government support under Grant No. AG020961d awarded by the National Institutes of Health. The government has certain rights in this invention. [0005] Background of the invention [0006] Muscle injuries are a very common phenomenon, ranging from relatively mild to extremely severe, and can take many forms. In addition, muscle damage is caused by a variety of reasons. For example, muscles are often accidentally injured during surgical procedures (eg, surgical therapy). This is especially evident in the case of surgical procedures such as caesarean section and joint replacement surgery ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/58A61K31/7068A61K45/06
CPCA61K38/1703A61K45/06A61K35/583A61K35/64A61P21/00A61K31/445A61K31/5575A61K2300/00A61P27/02A61P21/06A61K31/167A61K31/245A61K31/46A61K31/47A61K33/00A61K33/06A61K33/24A61K33/32A61K38/465A61K9/0019
Inventor 哈维·菲什曼凯瑟琳·柯廷克里斯托弗·佩恩斯科特·德尔普威威克·沙诺伊海伦·M·布劳安得烈·崔范何阿德莱达·R·帕拉
Owner THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV
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