Molecular therapy for Cardiomyopathy: Tetramethylpyrazine nitrone (TBN), a neuroprotective drug candidate for stroke, decreases the expression of Sox6, restores the balance between slow- and fast-twitch myofiber proteins and alleviates Cardiomyopathy via up regulation of its target gene, 5/December/2017,  11.55 pm

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Introduction: What they say

A recent study from the Department of Cardiology, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA; and Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts, USA shows that Trbp regulates heart function through microRNA-mediated Sox6 repression.” This study was published, in the 2 June  2015 issue of the journal “Nature Genetics” (the number 1 research journal in Genetics with an impact factor of 29.648), by Prof. Da-Zhi Wang & Jian Ding, and others


What we say:

On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Molecular therapy for Cardiomyopathy: Tetramethylpyrazine nitrone (TBN), a neuroprotective drug candidate for stroke, decreases the expression of Sox6, restores the balance between slow- and fast-twitch myofiber proteins and alleviates Cardiomyopathy via up regulation of its target gene


From significance of the study to public health relevance:

Given that: (1) cardiovascular disease is the leading cause of death worldwide; (2) Dilated cardiomyopathy is the leading cause of Heart failure; (3) the raise  of death rate, due to cardiovascular disease, has increased from 12.3 million in 1990 to 17.3 million in 2013; (4) 13% of cardiovascular disease occur due to  uncontrolled high blood pressure; (5) in India, in 2004, 14.6 lakhs deaths (14% of total deaths) were due to ischemic heart disease; (6) 85% of people over  80 years are susceptible to cardiovascular diseases; (7) the global economic cost spent in the treatment of cardiovascular disease in 2011 was little more than 10 billion US dollars; (8) the death due to cardiovascular disease is higher in low-to-middle income countries compared to developed countries; and (9) an alarming number of people, such as 230 lakhs people, will die from cardiovascular diseases each year by 2030, there is an urgent need to find:  (i) a cure to diseases, as mentioned above, leading to cardiovascular disease; (ii) a way to induce regeneration of adult cardiomyocytes that were lost in Myocardial patients; (iii) a cheaper alternative to the existing expensive drugs; and (iv) a side-effect-free Natural product-based drug.


What is known?

A number of studies suggests that Cardiomyopathy is the result of altered gene expression of contractile proteins. Trbp, an RNA binding protein, has been shown to be required for normal functioning of heart contractions.

Prof Da-Zhi Wang‘s research team has shown earlier that inactivation of Trbp in mice leads to progressive cardiomyopathy and heart failure. 


From research findings to Therapeutic opportunity: 

This study suggests, for the first time, that Tetramethylpyrazine nitrone (TBN) can be used in the treatment of Cardiomyopathy. This study suggests that Tetramethylpyrazine nitrone (TBN), by increasing the expression of its target gene, it may: (1) decrease the expression of Sox6; (2) increase the expression of cardiac slow-twitch myofiber proteins; (3) decrease the expression of skeletal fast-twitch myofiber proteins;  (4) restore the balance between slow- and fast-twitch myofiber proteins; and (5) alleviate cardiomyopathy (fig. 1).

Figure 1. Tetramethylpyrazine nitrone (TBN) as a cardioprotective agent. Tetramethylpyrazine nitrone (TBN), by increasing the expression of its target gene, it may decrease the expression of Sox6. Thereby, it may increase cardiomyocyte proliferation, augment the number of beating cardiomyocytes, and attenuate cardiomyopathy

 

Thus, pharmacological formulations encompassing “Tetramethylpyrazine nitrone (TBN) or its analogues, either alone or in combination with other drugs” may be used to inhibit progressive cardiomyopathy and lethal heart failure.


Details of the research findings:

Idea Proposed/Formulated byDr L Boominathan Ph.D.

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

Undisclosed mechanistic information: How 17α-Ethinylestradiol  inhibits the expression of Sox6.

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References:

Web: http://genomediscovery.org

To citeBoominathan, L., Molecular therapy for Cardiomyopathy: Tetramethylpyrazine nitrone (TBN), a neuroprotective drug candidate for stroke, decreases the expression of Sox6, restores the balance between slow- and fast-twitch myofiber proteins and alleviates Cardiomyopathy via up regulation of its target gene, 5/December/2017,  11.55 pm,  Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

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