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University of Florida to Genotype All Comers at Cath Lab to Personalize Treatment with Plavix, Eventually Other Drugs

Posted in Bio Instrumentation in Experimental Life Sciences Research, Biological Networks, Gene Regulation and Evolution, Cardiovascular Pharmacogenomics, Computational Biology/Systems and Bioinformatics, Genome Biology, Health Economics and Outcomes Research, HTN, Medical and Population Genetics, Origins of Cardiovascular Disease, Personalized and Precision Medicine & Genomic Research, Pharmaceutical Industry Competitive Intelligence, Pharmaceutical R&D Investment, Pharmacotherapy of Cardiovascular Disease, Population Health Management, Genetics & Pharmaceutical, Resident-cell-based, tagged , , , , , , , , , , , , on July 3, 2012| 1 Comment »

Reporter: Aviva Lev-Ari, PhD, RN

Moving Beyond Plavix PGx

Before it lost patent protection this year, clopidogrel was known under the brand name Plavix and marketed by Bristol-Myers Squibb. The Food and Drug Administration first updated the label for Plavix in 2009 to inform doctors that CYP2C19 poor metabolizers experienced diminished response to the drug and that PGx tests could be used to identify genotypes linked to variable treatment response. Then, in 2010, the FDA added a “black box” warning to Plavix’s label to highlight that poor metabolizers, or patients with the CYP2C19*2/*2 genotype, “exhibit higher cardiovascular event rates following acute coronary syndrome or percutaneous coronary intervention than patients with normal CYP2C19 function.” (PGx Reporter 3/17/2010)

Despite FDA’s vote of confidence in the association between certain CYP2C19 loss-of-function alleles and reduced response to Plavix, there is disagreement among healthcare providers about whether PGx testing in this setting is ready for broad implementation.

Scripps Health was an early adopter of PGx testing for Plavix. When in 2009, Scripps Health and Quest Diagnostics inked a deal to offer CYP2C19 testing to patients undergoing stent procedures, many doctors felt the program was premature given the evolving nature of the science (PGx Reporter 10/28/2009). The controversy has only gotten more contentious as several published meta-analyses have yielded conflicting results as to the validity of the association between genotype and drug response (PGx Reporter 3/28/2012).

The FDA has maintained that the available evidence supports its genetic testing recommendation for Plavix. In this regard, it is perhaps fitting that a forward-looking genetic testing program for Plavix is being launched at UF. Lawrence Lesko, former director of the Office of Clinical Pharmacology at FDA’s Center for Drug Evaluation and Research, who played a leadership role in adding PGx information to Plavix’s label, currently heads UF’s Center for Pharmacometrics and Systems Pharmacology and plays a leadership role in the university’s personalized medicine activities.

According to Johnson, UF launched its personalized medicine program with Plavix PGx testing because the black box warning on the drug’s label provided regulatory backing for implementing such testing. Additionally, “the things you potentially can impact with testing, such as major cardiovascular events, are clinically important,” she added. “We also felt that [since] the CYP2C19-clopidogrel effect is strongest in patients who are post percutaneous coronary interventions, that would allow us to focus on a very small patient population and a small number of physicians.”

Although UF’s genetic testing program is currently focused on cardiac patients who could potentially be treated with Plavix, the university has much bigger personalized medicine plans. “As we begin to roll out other pharmacogenomic indications [for cardiology patients] … we will also move past the cath lab … to the heart failure or electrophysiology clinic,” Johnson said, adding that the university intends to eventually implement genetic testing programs for gastroenterology patients.

“CYP2C19 testing for Plavix is just our starting point, so we can really work out the kinks, figure out how to educate the clinicians, figure out the barriers in a relatively confined setting,” she said. “But really, our goal is that we would run this chip on everybody presenting to the health system.”

http://www.genomeweb.com//node/1096991?hq_e=el&hq_m=1303351&hq_l=9&hq_v=e1df6f3681

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Macrovascular Disease – Therapeutic Potential of cEPCs: Reduction Methods for CV Risk

Posted in Bio Instrumentation in Experimental Life Sciences Research, Cell Biology, Signaling & Cell Circuits, Chemical Biology and its relations to Metabolic Disease, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Frontiers in Cardiology and Cardiovascular Disorders, Health Economics and Outcomes Research, HTN, Medical and Population Genetics, Nitric Oxide in Health and Disease, Origins of Cardiovascular Disease, Pharmaceutical Industry Competitive Intelligence, Pharmacotherapy of Cardiovascular Disease, Population Health Management, Genetics & Pharmaceutical, Resident-cell-based, tagged , , , , , , , on July 2, 2012| 29 Comments »

Macrovascular Disease – Therapeutic Potential of cEPCs: Reduction Methods for CV Risk

Curator: Aviva Lev-Ari, PhD, RN

An Investigation of the Potential of circulating Endothelial Progenitor Cells (cEPCs) as a Therapeutic Target for Pharmacological Therapy Design for Cardiovascular Risk Reduction: A New Multimarker Biomarker Discovery

Research Sources

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Heart Patients’ Skin Cells Turned into Healthy Heart Muscle Cells

Posted in Biological Networks, Gene Regulation and Evolution, Cell Biology, Signaling & Cell Circuits, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Frontiers in Cardiology and Cardiovascular Disorders, Genome Biology, Personalized and Precision Medicine & Genomic Research, Resident-cell-based, tagged on June 4, 2012| 3 Comments »

Heart Patients’ Skin Cells Turned into Healthy Heart Muscle Cells

Reporter: Aviva Lev-Ari, PhD, RN

 

In a scientific first, researchers at the Technion-Israel Institute of Technology have succeeded in taking skin cells from heart failure patients and reprogramming them to transform into healthy, new heart muscle cells capable of integrating with existing heart tissue.

The research, published online yesterday in the European Heart Journal, opens up the prospect of treating heart failure patients with their own, human-induced pluripotent stem cells (hiPSCs) to repair their damaged hearts. Since the reprogrammed cells would be derived from the patients themselves, the problem of the patients’ immune systems rejecting the cells as “foreign” could be avoided.  The researchers caution there are obstacles to overcome before it would be possible to use hiPSCs this way in humans, and it could take at least five to ten years before clinical trials could start.

“What is new and exciting about our research is that we have shown that it’s possible to take skin cells from an elderly patient with advanced heart failure and end up with his own beating cells in a laboratory dish that are healthy and young – the equivalent to the stage of his heart cells when he was just born,” said lead researcher Professor Lior Gepstein, of the Technion Faculty of Medicine, the Sohnis Research Laboratory for Cardiac Electrophysiology and Regenerative Medicine, and Rambam Medical Center.

Limor Zwi-Dantsis, a PhD student in the Technion’s Sohnis Research Laboratory, Prof. Gepstein, and their colleagues took skin cells from two male heart failure patients (aged 51 and 61) and reprogrammed them by delivering three genes or “transcription factors” (Sox2, Klf4 and Oct4), followed by a small molecule, called valproic acid, to the cell nucleus. It is important to note that this reprogramming cocktail did not include a transcription factor called c-Myc, which has been used for creating stem cells, but which is a known cancer-causing gene.

“One of the obstacles to using hiPSCs clinically in humans is the potential for the cells to develop out of control and become tumors,” explained Prof. Gepstein. “This potential risk may stem from several reasons, including the oncogenic factor c-Myc, and the random integration into the cell’s DNA of the virus that is used to carry the transcription factors – a process known as insertional oncogenesis.”

official news release issued by theEuropean Heart Journal, Thursday, May 24, 2012

http://www.ats.org/site/News2?page=NewsArticle&id=7359&news_iv_ctrl=1161

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