Use of tryptophan metabolites for treating muscle atrophy

A metabolite, tryptophan technology, applied in the field of tryptophan metabolites, can solve the problem of ineffective protein synthesis, and achieve the effect of improving recovery time and increasing muscle mass

Pending Publication Date: 2019-06-28
METABRAIN RES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] However, there is no literature describing or proposing that tryptophan metabolites selected from kynurenic acid, anthranilic acid, quinolinic acid, picolinic acid and quinalcolic acid can have a posit

Method used

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  • Use of tryptophan metabolites for treating muscle atrophy
  • Use of tryptophan metabolites for treating muscle atrophy
  • Use of tryptophan metabolites for treating muscle atrophy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0067] Example 1: Measurement of protein synthesis in C2C12 cells

[0068] Cells were counted and seeded at a density of 20 000 cells per well in 24-well plates in DMEM supplemented with fetal calf serum (10%) and antibiotics (penicillin and streptomycin) containing glucose at a ratio of 4.5 g / l medium. After 48 hours, myoblast differentiation was induced for 5 days by partial serum deprivation (2% instead of 10%). The cells were then placed in medium without glucose or leucine (Krebs medium) at 37°C for 1 h, and then in serum-free DMEM medium containing 2.5 μCi / ml radiolabeled leucine, at In the presence of the product to be tested (DMSO (control), kynurenic acid or anthranilic acid or quinolinic acid or picolinic acid or 3OH-kynurenine) or reference (IGF-1, 100 ng / ml) Warm bath for 150min. At the end of the incubation, the supernatant was removed and the cells were lysed in 0.1 N NaOH solution for 30 min. Radioactivity was measured in the cellular fraction and the total ...

Embodiment 2

[0069] Example 2: Measurement of Myostatin Gene Expression in C2C12 Cells

[0070] C2C12 myoblasts (ATCC CRL-1772) were seeded in 24-well plates at a density of 30 000 cells per well in a cultured medium containing glucose at a ratio of 4.5 g / l supplemented with fetal calf serum (10%) and antibiotics cultured in DMEM medium (penicillin and streptomycin). After 48 hours, the myoblasts were induced to differentiate for 5 days by partial serum deprivation (2% instead of 10%). Cells were then placed in serum-free, glucose-depleted medium (DMEM containing 1 g / l glucose) in the presence of the molecule to be tested (DMSO (control) or IGF-1 (100 ng / ml) or kynurenic acid ) or reference (IGF-1 at a concentration of 100ng / ml) for 6h. At the end of the experiment, messenger RNA (mRNA) was extracted using conventional methods based on phenol and chloroform. Briefly, cells were lysed in trizol solution (Sigma T9424) containing strong acid and phenol. mRNA was separated from protein by ...

Embodiment 3

[0075] Example 3: Evaluation of C2C12 muscle fiber diameter

[0076]C2C12 myoblasts (ATCC CRL-1772) were seeded at a density of 10 000 cells per well in glycerol-treated 8-well plates in the presence of glucose at a ratio of 4.5 g / l supplemented with fetal bovine serum (10 %) and antibiotics (penicillin and streptomycin) in DMEM medium. After 48 hours, the myoblasts were induced to differentiate for 3 days by partial serum deprivation (2% instead of 10%). Cells were then placed in serum-free, glucose-depleted medium (DMEM containing 1 g / l glucose) in the presence of the molecule to be tested (DMSO (control) or kynurenic acid) or reference (at a concentration of 100 ng / l ml of IGF-1 or 10 μM dexamethasone) for 3 days. At the end of the incubation, cells were washed and fixed using a 2.5% glutaraldehyde / 0.1% triton solution for 1 h at ambient temperature. The cell layer was overlaid with DAPI, a fluorescent marker of the nucleus. After being stored in a dark place for 16 hou...

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Abstract

The present invention concerns a tryptophan metabolite chosen from kynurenic acid, anthranilic acid, quinolinic acid, picolinic acid, quinaldic acid and the mixtures of same or an enantiomer, diastereoisomer, hydrate, solvate, tautomer, racemic mixture or pharmaceutically acceptable salt of same, for use as a drug intended for increasing and/or maintaining muscle mass and/or strength in a mammal,and in particular intended for treating and/or preventing muscle atrophy in mammals and/or for promoting muscle growth in mammals doing exercise and aiming to increase muscle mass and/or quality and/or strength, for preventing the appearance of symptoms of sarcopenia or for rehabilitation following muscle loss and/or for improving recovery time after an intense physical effort.

Description

technical field [0001] The present invention relates to tryptophan metabolites for the treatment and prevention of diseases associated with muscle wasting. Background technique [0002] From a functional point of view, muscle strength (ability to maintain maximal contraction levels during sustained exertion) and muscle mass (per unit of muscle mass) measures of force) are important, and they may be worse with the situation, for example in certain diseases associated with muscle weakness or wasting (cachexia, sarcopenia, sarcopenic obesity, cancer, Duchenne muscular dystrophy ( DMD), amyotrophic lateral sclerosis (ALS), myotonic dystrophy (MDA), heart failure, etc.) or during muscle damage following strenuous physical exertion. Changes in the isokinetic endurance factor (the ratio of the force of the last three concentric muscle contractions relative to the first three) and loss of muscle strength are usually good indicators regardless of the circumstances. [0003] Aging o...

Claims

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Application Information

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IPC IPC(8): A61K31/47A61P21/00
CPCA61K31/47A61P21/00A61K31/196A61K9/0053
Inventor S·N·雷尔内A·奥黛V·奥蒂耶C·沙隆J-D·杜朗M·喀尔哥特
Owner METABRAIN RES
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