Atrasentan-based Regenerative therapy for regaining the lost cardiomyocytes in Myocardial patients: Atrasentan, an endothelin receptor antagonist selective for subtype A (ETA) used to treat cancer, pulmonary hypertension, diabetic kidney diseases and others, increases the expression of ERBB2/Her2 and promotes dedifferentiation  of cardiomyocytes, via up-regulation of its target gene, 20/May/2019, 12.39 am

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Introduction: What they say

A recent study from the Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel shows that “ERBB2 triggers mammalian heart regeneration by promoting cardiomyocyte dedifferentiation and proliferation.” This study was published, in the 6 April  2015 issue of the journal “Nature cell biology” (the number 1 journal in “Cell biology” research with an impact factor of 20+)by Prof Tzahor E, D’Uva E, and others.


What we say: 

On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Atrasentan-based Regenerative therapy for regaining the lost cardiomyocytes in Myocardial patients: Atrasentan, an endothelin receptor antagonist selective for subtype A (ETA) used to treat cancer, pulmonary hypertension, diabetic kidney diseases and others, increases the expression of ERBB2/Her2 and promotes dedifferentiation  of cardiomyocytes, via up-regulation of its target gene


From the significance of the study to Public health relevance: 

Given that: (1)  cardiovascular disease is the leading cause of death worldwide; (2) the raise of death rate, due to cardiovascular disease, has increased from  123 lakhs in 1990 to 173 lakhs in 2013; (3) 85% of people over 80 years are susceptible to cardiovascular diseases;(4) in India, in 2004, 14.6 lakhs deaths (14% of total deaths) were due to ischemic heart disease; (3) the death due to cardiovascular disease is higher in low-to-middle income countries compared to developed countries; (4) the global economic cost spent in the treatment of cardiovascular disease in 2011 was little more than 10 billion US dollars; (5) 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 way to induce regeneration of cardiomyocytes that were lost in Myocardial patients; (ii) a cheaper alternative to the existing expensive drugs and (iv) a side-effect-free Natural product-based drug.

 


From research findings to Therapeutic opportunity: 

I had suggested earlier  on 21/January/2018  that Atrasentan  may improve metabolic abnormalities, albuminuria, glomerular pathology, and renal dysfunction and alleviate diabetic nephropathy  (https://genomediscovery.org/2018/01/molecular-therapy-for-diabetic-nephropathy-dn-atrasentan-a-drug-used-in-the-treatment-of-diabetic-kidney-disease-and-cancer-increases-pyruvate-kinase-m2-pkm2-expression-decreases-tox). Evidently, a very recent study from the Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands and others shows that “Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease.” This study was published, in the 12 April 2019 issue of of the prestigious journal Lancet (Impact factor: 53.254),  by Prof. De Zeeuw D, Heerspink HJL, and others. In concordance with what I stated earlier, this study suggests that atrasentan may protect renal function in  patients with type II diabetes .  However, the mechanism of action of this drug is not known yet.  

This study provides, for the first time, mechanistic insights into how Atrasentan, which is used to treat cancer, pulmonary hypertension, diabetic kidney diseases and others, may aid in heart regeneration and repair.

This study suggests, for the first time,that how Liraglutide may protect against cardiovascular diseases and aid in cardiac regeneration.  Canagliflozin, by regulating the expression of its target genes, it may: (1) increase ERBB2/Her2 expression; (2) induce cardiomyocyte (CM) dedifferentiation and proliferation; and (3) cardiomyocyte (CM) redifferentiation and regeneration (fig.1).  Thus, pharmacological formulations encompassing“Liraglutide  or its analogs, either alone or in combination with other drugs,” may be used to promote cardiac dedifferentiation and regeneration.

Figure1. Mechanistic insights into how atrasentan may promote cardiac dedifferentiation and regeneration. Atrasentan, by increasing the expression of its target genes, it may upregulate the expression of ERRB2/HER2 and promote cardiac dedifferentiation and regeneration

Figure 2. Atrasentan may promote cardiac regeneration through induction of Her2/Erbb2

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Given the mechanistic basis of how Atrasentan may aid in cardiomyocyte survival and regeneration,  medical practitioners and cardiologists may consider treating myocardial patients with Atrasentan, as it may aid in cardiomyocyte regeneration following myocardial infarction

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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/

Amount: $ 500#

Undisclosed (mechanistic insights) information: How does  atrasentan increase the expression of  ERBB2/Her2?

For purchase and payment details, you may reach us at admin@genomediscovery.org

# Research cooperation


References: 

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

Citation: Boominathan, L.,  Atrasentan-based Regenerative therapy for regaining the lost cardiomyocytes in Myocardial patients: Atrasentan, an endothelin receptor antagonist selective for subtype A (ETA) used to treat cancer, pulmonary hypertension, diabetic kidney diseases and others, increases the expression of ERBB2/Her2 and promotes dedifferentiation  of cardiomyocytes, via up-regulation of its target gene, 20/May/2019, 12.39 am,  Genome-2-BioMedicine Discovery center (GBMD), http://genomediscovery.org

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