Bacillus Calmette Guerin (BCG)/tuberculosis (TB) vaccine aids in the treatment of Deafness: BCG/TB vaccine increases the expression of ATG5 (Autophagy-related 5), prevents aggregation of proteins in inclusion bodies, inhibits hair cell degeneration,  improves hearing loss via upregulation of its target genes, 1/August/2018, 2.10 pm

What we say:

Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that:  Bacillus Calmette Guerin (BCG)/tuberculosis (TB) aids in the treatment of Deafness: BCG/TB vaccine increases the expression of ATG5 (Autophagy-related 5), prevents aggregation of proteins in inclusion bodies, inhibits hair cell degeneration,  improves hearing loss via upregulation of its target genes

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From Significance of the study to Public health relevance:

Given that: (1) more than one seventh of the global population suffers from hearing impairment;  (2) majority of hearing impairment occurs in  low and middle income countries, for instance, 3 in 1000 from developed countries, while 6 in 1000 from developing countries suffer from hearing impairment; (3) damage to the auditory hair cells (HCs) is the principal reason for hearing loss;  (4) only in 50% cases hearing impairment can be cured; and (5) the global annual economic cost spent for unaddressed hearing loss is estimated to be in the range of $750–790 billions, there is an urgent need to find: (i) a way to promote regeneration, growth and proliferation of auditory hair cells  in mammalian cochlea; (ii) a cheaper alternative to the existing expensive drugs; (iii) a side-effect-free natural product-based drug; and (iv) a way to cure, not just treat, hearing impairment.

From 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 hearing loss. 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.

BCG/TB vaccine, by increasing the expression of its target genes, it may increase the expression of ATG5 (Autophagy-related protein 5). Thereby, it may: (1) prevent degeneration of adult hair cells; (2) prevent aggregation of polyubiquitinated proteins and p62/SQSTM1 in inclusion bodies; (3) promote maintenance of hair cells morphology and hearing acuity; and (4) prevent hearing loss. Thus, BCG/TB vaccine, either alone or in combination with other drugs, may be used to treat deafness (Fig.1).

Figure 1 Mechanistic insights into how BCG/TB vaccine aids in improving hearing impairment. BCG/TB vaccine prevents aggregation of proteins, promotes regeneration of adult hair cells, and inhibits hearing impairment, via up-regulation of its target gene ATG5

Figure 2. The TB/BCG vaccine protects against hearing loss through induction of ATG5.

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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 BCG/TB vaccine increase the expression of ATG5?

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References:

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Citation: Boominathan, L.,Bacillus Calmette Guerin (BCG)/tuberculosis (TB) aids in the treatment of Deafness: BCG/TB vaccine increases the expression of ATG5 (Autophagy-related 5), prevents aggregation of proteins in inclusion bodies, inhibits hair cell degeneration,  improves hearing loss via upregulation of its target genes, 1/August/2018, 2.10 pm, Genome-2-BioMedicine Discovery center (GBMD), http://genomediscovery.org

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