Introduction: What they say
A study from the Laboratory of Obesity and Aging Research, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA; and Laboratory of Obesity and Aging Research, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA shows that “DNA-PK Promotes the Mitochondrial, Metabolic, and Physical Decline that Occurs During Aging.” This research paper was published, in the 2 May 2017 issue of the journal “Cell Metabolism” [One of the best research journals in Metabolism research with an I.F of 17.303], by Prof. Chung JH and Park SJ and others.
What we say:
On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Repurposing the tuberculosis vaccine into a diabetic vaccine: TB/BCG vaccine, a tuberculosis vaccine, decreases DNA-PPK expression, suppresses phosphorylation of HSP90a, increases AMPK activity, augments mitochondrial biogenesis and energy metabolism, promotes weight loss and exercise endurance and alleviates TIIDM via down-regulation of its target gene
The significance of the study:
Given that: (1) more than 387 million people worldwide are affected by Diabetes mellitus (DM); (2) Diabetes is going to be one of the top 10 causes of death by 2030; (3) the life-long painful injection/drug treatment is required to treat DM; (3) the global economic cost spent for diabetes treatment in 2014 was little more than 600 billion US dollars, there is an urgent need to find: (i) a way to induce regeneration of adult ß-cells that were lost in DM; (ii) a cheaper alternative to the existing expensive weight-loss drugs; (iii) a side-effect-free natural product-based drug; and (iv) a way to cure, not just treat, diabetes.
What is known?
Prof. Chung JH’s research team has recently shown that as ageing increases DNA breaks occur more frequently and activation of DNA-dependent protein kinase (DNA-PK) occur which results in:(1) decreased mitochondrial function, metabolism and physical fitness; (2) increased phosphorylation of HSP90a; (3) decreased chaperone function toward its client protein such as AMP-activated protein kinase (AMPK); and (4) compromised mitochondrial biogenesis and energy metabolism. Conversely, decreasing DNA-PK results in (1) increased AMPK activity; (2) weight loss; and (3) protection against TIIDM, suggesting that decreasing the expression of DNA-PK in middle-aged diabetic patients may alleviate TIIDM and increase exercise endurance.
Research findings to Therapeutic opportunity:
This study suggests, first the first time, Bacillus Calmette Guerin (BCG) vaccine-based therapy, with detailed mechanistic insights, for diabetes. 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 gene, it may decrease the expression of DNA-PK. Thereby, it may: (1) decrease phosphorylation of HSP90a; (2) increase AMPK activity; (3) increase mitochondrial biogenesis and energy metabolism; (4) increase insulin sensitivity; (5) increase exercise endurance; (6) augment weight loss; and (7) protect against TIIDM (Fig.1).
Thus, TB/BCG vaccine, either alone or in combination with other drugs,” may be used to treat middle-aged Obese TIIDM patients.
Details of the research findings:
Idea Proposed/Formulated (with experimental evidence) by Dr L Boominathan Ph.D.
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Undisclosed mechanistic information: How does TB/BCG vaccine decrease the expression of DNA-PK to promote insulin sensitivity?
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Citation: Boominathan, L., Repurposing the tuberculosis vaccine into a diabetic vaccine: TB/BCG vaccine, a tuberculosis vaccine, decreases DNA-PPK expression, suppresses phosphorylation of HSP90a, increases AMPK activity, augments mitochondrial biogenesis and energy metabolism, promotes weight loss and exercise endurance and alleviates TIIDM via down-regulation of its target gene, 23/July/2018, 11.14 am, Genome-2-BioMedicine Discovery center (GBMD), http://genomediscovery.org