Amino-acid based therapy for Inflammatory bowel disease: Leucine, the branched chain amino acid, decreases the expression of oncostatin M, attenuates activation of oncostatin M- oncostatin M receptor pathway in inflamed colon tissues, inhibits inflammatory gene expression, attenuates colonic pathogenesis, and inhibits the progression of inflammatory bowel disease and colitis via down regulation of its target gene, 22/May/2017, 11.50 pm

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Introduction: What they say:

A study from the Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK shows that “Oncostatin M drives intestinal inflammation and predicts response to tumor necrosis factor–neutralizing therapy in patients with inflammatory bowel disease”. This study was published, in the 28 April 2017 issue of the journal “Nature Medicine” (one of the best research journal in “General medicine” with an impact factor of 30.357), by Prof. Fiona Powrie, Nathaniel R West and others.


What we say:

On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Amino-acid based therapy for Inflammatory bowel disease:  Leucine, the branched chain amino acid, decreases the expression of oncostatin M, attenuates activation of oncostatin M- oncostatin M receptor pathway in inflamed colon tissues, inhibits inflammatory gene expression, attenuates colonic pathogenesis, and inhibits the progression of inflammatory bowel disease and colitis via down regulation of its target gene

 


What is known?

Inflammatory bowel disease (IBD), which includes ulcerative colitis, is characterized by infiltration of T-cells that damage colon.

Prof. Fiona Powrie’s research team has recently shown that: (1) cytokine oncostatin M and its receptor are overexpressed in patients with inflammatory bowel disease (IBD); (2) overexpression of oncostatin M and its receptor  correlate with disease severity; and unresponsiveness to anti-TNF therapy; (3) increased activation of oncostatin M and its receptor  pathway results in increased expression of proinflammatory molecules, including IL-6, the leukocyte adhesion factor ICAM1 and chemokines; (4) knock down or inhibition of OSM results in reduction of colonic chemokine and proinflammatory cytokine production and alleviation of IBD, suggesting that OSM inhibitors may be used to inhibit the progression of IBD, particularly in patients nonresponsive to anti-TNF therapy.


From Significance of the study to Public health relevance:

Given that: (1) about 5 million people worldwide suffer from inflammatory bowel disease (IBD); (2) 1 million people suffer from IBD in the US, while in Europe 2.5 million; (2) IBD is more common in westernized nations, including North america and Europe, and in industrialized countries; (3) the incidence of colitis and inflammatory bowel disease is on the rise globally, (4) about 40% of patients, which translates to about 2 million people worldwide, are resistant to Anti-tumor necrosis factor-a (TNF) antibodies-the mainstay therapy for IBD, (5) molecular pathways involved and the mechanism of development of inflammatory bowel disease is far from understood; (6) substantial amount is spent each year globally for the treatment of colitis and inflammatory bowel disease, there is an urgent need to find: (i) a way to cure colitis and inflammatory bowel disease; (ii) a cheaper alternative to the existing expensive drugs; and (iii) a side-effect-free-Natural product-based drug that permanently cures, not just treats, colitis and treatment-resistant inflammatory bowel disease.


From Research Findings to Therapeutic opportunity:

This study suggests an amino acid-based therapy for inflammatory bowel disease and colitis.

Leucine, by regulating the expression of its target genes, it may: (1) decrease the expression of cytokine oncostatin M  and its receptor; (2) inhibit the expression of pro-inflammatory genes, including IL-6, the leukocyte adhesion factor ICAM1 and chemokines; (3) suppress colonic pathogenesis; and (4) stall the progression of inflammatory bowel disease and colitis (fig.1).

Figure 1. Mechanistic insights into how the branched chain amino acid L-Leucine may aid in prevention of inflammatory bowel disease and colitis. Leucine, by increasing the expression of its target gene, decrease the expression of cytokine oncostatin M and its receptor, decrease the expression of pro-inflammatory genes. and inhibit the progression of inflammatory bowel disease and colitis.

Together, pharmacological formulations encompassing “Leucine or its analogues, either alone or in combination with other drugs”, may be used to treat inflammatory bowel disease and colitis.

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Details of the research findings:

Idea Proposed/Formulated by: Dr L Boominathan Ph.D.

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

Undisclosed mechanistic information: How Leucine inhibits the expression of Oncostatin-M to inhibit the progression of inflammatory bowel disease and colitis

Amount: $500#

# Research cooperation


References:

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

Citation: Boominathan, L., Amino-acid based therapy for Inflammatory bowel disease:  Leucine, the branched chain amino acid, decreases the expression of oncostatin M, attenuates activation of oncostatin M- oncostatin M receptor pathway in inflamed colon tissues, inhibits inflammatory gene expression, attenuates colonic pathogenesis, and inhibits the progression of inflammatory bowel disease and colitis via down regulation of its target gene, 22/May/2017, 11.50 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

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