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Introduction: What they say

A study from Department of Biology, University of Bergen, Bergen, Norway; and Univ-Lyon, CarMeN Laboratory, INSERM 1060, INRA 1397, Université Claude Bernard Lyon, INSA Lyon, Oullins, France shows that FGF19 regulates skeletal muscle mass and ameliorates muscle wasting in mice. This research paper was published, in the 26 June 2017 issue of the journal “Nature Medicine” [One of the best research journals in Biology with an I.F of 29 plus], by Prof.Ruzzin J, Bérengère B, and others.


What we say:

On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Unknown function of a known vaccine in the treatment of muscle atrophy and wasting: TB/BCG vaccine,  a tuberculosis vaccine,  increases the expression of FGF19 and its receptor ß-Klotho, phosphorylates ERK1/2 and S6K1, decreases the expression of tumor suppressors  genes, promotes regeneration of muscle cells and hypertrophy of skeletal muscle, and reverses muscular atrophy and wasting, via upregulation of its target gene from


Significance of the study to Public health relevance:

Given that: (1) Muscular dystrophy/wasting is a degenerative disease; (2) Muscular dystrophy/wasting also occur due to a number of pathophysiological conditions, including cancer, denervation, disuse, and fasting ; (3) there is no permanent cure for muscular dystrophy; (4) the life-long discomfort and the medical care required to alleviate pain-associated (muscle weakness) with muscular dystrophy; (5) the global economic cost spent for muscular dystrophy is enormous,there is an urgent need to find: (i) a way to rejuvenate muscle (satellite) stem cells that were lost in Muscular dystrophy; (ii) a cheaper alternative to the existing expensive drugs; and (iii) a side-effect-free natural product-based drug.


What is known?

A number of studies have firmly established a role for FGF19 in metabolic diseases. However, its role in other physiological processes remains largely unknown.

Prof. Ruzzin’s research team members have recently shown that:(1) FGF19 treatment results in skeletal muscle hypertrophy; (2) treatment with physiologically equivalent level of FGF19 increases the size of human myotubes; (3) induction of FGF19 results in phosphorylation of extracellular-signal-regulated protein kinase 1/2 (ERK1/2) and the ribosomal protein S6 kinase (S6K1), a protein that promotes protein synthesis and cell growth ; (4) deletion of ß-Klotho (KLB), a receptor of FGF19, in skeletal muscle nullifies the hypertrophic actions of FGF19; (5) treatment with FGF19 improves skeletal muscle atrophy caused by a) glucocorticoid treatment, b) obesity, and c)sarcopenia, suggesting that increasing the expression of FGF19 may prevent muscle wasting, attenuate muscular dystrophy and improve sarcopenia.


Research findings to Therapeutic opportunity:

This study suggests, first the first time, a Bacillus Calmette Guerin (BCG) vaccine-based regenerative therapy, with detailed mechanistic insights, for muscular dystrophy and wasting. BCG vaccine has been found to be useful in the treatment of tuberculosis, for more than 100 years, more recently in the treatment of autoimmune diabetes. However, the mechanism of action remains largely unknown.

TB/BCG vaccine, by increasing the expression of its target genes, it may increase the expression of FGF19 and its receptor ß-Klotho (KLB) (Fig. 1). Thereby, it may: (1) increase the phosphorylation of ERK1/2 and S6K1; (2) enlarge muscle fiber size; (3) increase skeletal muscle mass; (3) promote skeletal muscle hypertrophy; (4) protect muscle from atrophy and muscle wasting. Thus, TB/BCG vaccine, either alone or in combination with other drugs”, may be used to treat muscular dystrophy and wasting (fig.1).

Given the mechanistic insights as to how TB/BCG vaccine may aid in the treatment of muscular dystrophy,  physicians may consider: vaccinating their muscular dystrophic patients with  TB/BCG vaccine or beginning a clinical trial. 

Figure 1.Mechanistic insights into how TB/BCG vaccine protects against Muscular dystrophy and wasting.  TB/BCG vaccine, by increasing the expression of FGF19 and its downstream target genes, may promote muscle hypertrophy and ameliorate muscular dystrophy.

Figure 2. Repurposing the tuberculosis vaccine into a muscular dystrophy vaccine.

 

Details of the research findings:

Idea Proposed/Formulated (with experimental evidence) by Dr L Boominathan Ph.D.

Terms & Conditions apply http://genomediscovery.org/registration/terms-and-conditions/

Undisclosed mechanistic information: How does TB/BCG vaccine increase the expression of FGF19?

Amount: $ 500#

# Research cooperation

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References:

Web: http://genomediscovery.org or http://newbioideas.com

Terms & Conditions apply http://genomediscovery.org/registration/terms-and-conditions/

Citation: Boominathan, L., Unknown function of a known vaccine in the treatment of muscle atrophy and wasting: TB/BCG vaccine,  a tuberculosis vaccine,  increases the expression of FGF19 and its receptor ß-Klotho, phosphorylates ERK1/2 and S6K1, decreases the expression of tumor suppressors  genes, promotes regeneration of muscle cells and hypertrophy of skeletal muscle, and reverses muscular atrophy and wasting via upregulation of its target gene, 25/July/2018, 11.48 pm, Genome-2-BioMedicine Discovery center (GBMD), http://genomediscovery.org

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