Carmel Valley-based scientists among local scientists who use dynamic medicinal chemistry to help cardiac regeneration

Scientists at the Human BioMolecular Research Institute (HBRI) in San Diego and Sanford-Burnham Medical Research Institute (Sanford-Burnham) in La Jolla, and ChemRegen, Inc., a San Diego for-profit company focused on developing small-molecule regenerative medicines for human diseases, have reported on a new set of small molecules helpful in human cardiomyocyte formation using inhibition of a biochemical signaling pathway called Wnt.

The Wnt signaling pathway is a key mediator of cellular development and stem cell differentiation. A paper published online* in the Journal of Medicinal Chemistry reports a new class of small molecules that work as Wnt inhibitors that can be used to increase cardiogenesis from human stem cells.

In the United States, curing heart disease is a major unmet medical need.  Of the 300,000 individuals suffering from heart disease that need a heart transplant, less than 1 percent will receive one. During a heart attack, heart tissue is irreparably damaged and scar tissue can form around the heart that may eventually lead to heart failure. If regenerative medicine could provide a way to regenerate damaged tissue, it would be a significant benefit to millions of people who are currently living with heart disease.  Another application of the technology is to generate large numbers of cardiomyocyte cells for transplantation purposes.

Scientists at HBRI and Sanford-Burnham, in collaboration with ChemRegen, chemically synthesized and tested a large number of small molecules that induce cardiogenic differentiation.  In this series of small molecules, they found that the potency of Wnt inhibition highly correlates with the ability of the molecules to cause cardiogenesis.

Some of the most promising small molecules identified may be useful for making large numbers of human cardiomyocytes. The most potent Wnt inhibitors discovered have also increased our understanding of the biology underlying the process. One potent small molecule was identified that inhibited transduction of the canonical Wnt response within the cell, showing that Wnt inhibition alone is sufficient for deriving cardiomyocytes from human embryonic stem cells (hESCs) originating from mesoderm cells. This may have practical applications for making large numbers of cells for utility in a biotechnology sense from hESCs because there are currently few ways to readily make large numbers of human heart cells.

The dynamic medicinal chemistry research approach used in these studies represents an exciting new paradigm to discover therapies for heart disease, and may result in drug leads for human cardiac regeneration or practical approaches for producing large numbers of human cardiomyocytes.

For more information, visit www.HBRI.org; www.sanfordburnham.org; visit www.ChemRegen.com.

*M Lanier, D Schade, E Willems, M Tsuda, S Spiering, J Kalisiak, M Mercola and JR Cashman. (2012) Wnt Inhibition Correlates with Human Embryonic Stem Cell Cardiomyogenesis: A Structure−Activity Relationship Study Based on Inhibitors for the Wnt Response.  J. Med Chem. January 12 (Epub ahead of print).

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Short URL: http://www.delmartimes.net/?p=30909

Posted by Staff on Jan 23, 2012. Filed under Carmel Valley, News, carmel valley. You can follow any responses to this entry through the RSS 2.0. You can leave a response or trackback to this entry

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