Summary of research progress in the field of cardiovascular disease (12.08)
December 08, 2017 Source: WuXi PharmaTech
Window._bd_share_config={ "common":{ "bdSnsKey":{ },"bdText":"","bdMini":"2","bdMiniList":false,"bdPic":"","bdStyle":" 0","bdSize":"16"},"share":{ }};with(document)0[(getElementsByTagName('head')[0]||body).appendChild(createElement('script')) .src='http://bdimg.share.baidu.com/static/api/js/share.js?v=89860593.js?cdnversion='+~(-new Date()/36e5)];1. Effective prevention of heart disease and stroke, Amgen new drugs approved by the US FDA
Recently, Amgen announced that the US FDA has approved its new drug Repatha (evolocumab) supplemental biologics license application (sBLA) to help adults with cardiovascular disease prevent heart disease, stroke, and coronary revascularization. This is the first PCSK9 inhibitor approved for these diseases.
According to the US CDC, heart disease is the first killer of the Americans, and stroke is the fifth leading cause of death. The number of people who die from these two diseases is nearly 800,000 a year, which brings more than $600 billion a year to society.
The FDA approved evolocumab is a human monoclonal antibody that binds to and inhibits PCSK9 protein. In humans, PCSK9 proteins bind low-density lipoprotein (LDL) receptors and contribute to the degradation of these receptors. Inhibition of PCSK9 allows the LDL receptor to return to the surface of the liver cells, thereby reducing the amount of LDL in the blood. In 2015, it was approved by the US FDA to treat patients with high cholesterol who could not control their condition through existing therapies.
The mechanism of action of Evolocumab demonstrates the potential to prevent cardiovascular disease and was validated in an international Phase 3 clinical trial called FOURIER, with a total of 27,564 patients enrolled in the study. The study found that adding evolocumab to optimized statin therapy significantly reduced the risk of major adverse cardiovascular events (MACE) by 20% (p < 0.001). In a single case, the therapy reduced the risk of heart disease by 27% (nominal p < 0.001), 21% risk of stroke (nominal p = 0.01), and 22% risk of coronary revascularization (nominal p < 0.001). Fortunately, overall, over time, the preventive effect of the therapy will get better and better: the researchers found that patients can get a significant and significant increase in the first six months.
â–² Dr. Sean E. Harper, Executive Vice President of R&D, Anjin (Source: Anjin official website)
“We are very pleased to see that the FDA has prioritized our data to enable patients to benefit from Repatha and reduce the incidence of heart disease and stroke events that can change lives,†said Dr. Sean E. Harper, Executive Vice President of Research and Development at Amgen. "Despite the best treatment available, many patients are still at high risk of cardiovascular events. Doctors now have an FDA-approved new treatment that prevents cardiovascular disease by significantly lowering LDL cholesterol levels. Incidents. This can help those who have the greatest tolerance to statin therapy to further lower LDL cholesterol levels."
2. Accelerate the development of new drugs for hypertension, Yang Sen reached a large cooperation of 230 million US dollars
Recently, Johnson & Johnson's Janssen announced a cooperation agreement with Idorsia to jointly develop and promote the high-pressure drug aprocitentan and its derivative compounds.
In January of this year, Johnson & Johnson acquired Actelion in Switzerland. As part of the agreement, Actelion split its drug discovery and early R&D department into a new company called Idorsia, which is dedicated to bringing more innovative drugs to patients. Aprocitentan, an oral dual endothelin receptor antagonist, is a high blood pressure drug in the company. The phase 2 clinical trial achieved positive results in May this year: after 8 weeks of treatment with aprocitentan, the diastolic blood pressure was reduced by 6.3 mmHg and 12.0 mmHg compared with the placebo and lisinopril groups, respectively. The drug is currently undergoing the design of Phase 3 clinical trials.
Under the cooperation agreement, Janssen will pay Idorsia a one-time milestone payment of $230 million. Yang Sen and Idorsia will have joint development rights. Idorsia handles Phase 3 drug development and regulatory submissions, and Janssen manages Phase 3 R&D and submission of any other indication.
â–² Dr. Martine Clozel, Chief Scientific Officer of Idorsia (Source: Ivorsia Official Website)
"This decision indicates that Janssen has recognized the potential of aprocitentan, the latest product of a study that began nearly 30 years ago and has a broad understanding of the endothelin system and two endothelin receptor antagonists on the market." Dr. Martine Clozel, Chief Scientific Officer of Idorsia, said: "In addition to high blood pressure, aprocitentan has many other potential applications. This makes the cooperation with Janssen more meaningful to us."
3. Duke engineers create a full-featured beating heart patch
After a heart attack, the dead heart muscle is replaced by an intractable scar tissue, leading to chronic heart failure. Chronic heart failure is affecting the health of 12 million people in the world. Regeneration of damaged heart tissue is a challenging task: the heart muscle must be able to contract spontaneously and must be able to transmit electrical signals.
Engineers at Duke University said they created an artificial myocardium that could be used to compensate for myocardial damage in heart patients. They have in vitro cultured human pluripotent stem cells that can be transformed into any tissue type to achieve this. The researchers were able to grow the myocardial patches to the appropriate size within five weeks and allow them to pulsate at the beating intensity of normal adult hearts. They tested the invention in a rodent model and found that the patch survived, formed blood vessels and maintained its function. The study was published in Nature, a journal in Nature.
The researchers tested different combinations of cells, nutrients and growth factors. They found that shaking cells growing in the nutrient solution during cell culture resulted in larger, thicker sections of myocardial tissue. The author of the paper, Dr. Nenad Bursac, professor of biomedical engineering at Duke University, said at the press conference: “It is very difficult to do this because the larger the growing tissue, the harder it is to maintain consistent performance across the organization.†In addition, ensuring that the performance of the patch is as challenging as the heart of an adult, because humans usually require years of normal development to achieve these characteristics.
â–² Dr. Nenad Bursac, Professor of Biomedical Engineering at Duke University (Source: Duke University Official Website)
Scientists are exploring a variety of techniques to regenerate damaged hearts using human cells, including direct injection of stem cells into damaged myocardium. This summer, a team of professors at Boston University, Professor Christopher S. Chen, invented a 3D printed patch that promotes healthy blood vessel growth in ischemic tissue for repair of lower limb ischemia or myocardial ischemia. In addition, scientists at the University of Toronto are developing a patch that can be folded into a syringe and injected into the damaged heart.
The research team led by Bursac believes that to make a truly effective heart patch, the size is important, and the patch they invented is large enough to repair the heart's damage. However, these patches need to be further optimized before clinical testing to a greater extent than used in the study. Their next challenge will be to make thicker patches that will be vascularized so that they get enough nutrients and oxygen to integrate them with existing healthy myocardium.
Ilia Shadrin, a Ph.D. student in biomedical engineering at Duke University, said: "Complete integration like this is very important. (Treatment of myocardial ischemia) not only needs to improve the mechanical pumping of the heart, but also to ensure the heart. Smooth propagation of radio waves and minimizing the risk of arrhythmia.
Reference material
[1] FDA Approves Amgen's Repatha® (evolocumab) To Prevent Heart Attack And Stroke
[2] Little Idorsia Scores $230M+ R&D Deal With Johnson & Johnson
[3] Duke engineers create fully functional beating heart patch
Original Title: Summary of Research Progress in the Field of Cardiovascular Diseases (No. 23)
To extract a mixture of DNA fragments, put through a PCR instrument to do a simple purification. Remove the free fluorescent ddNTP single nucleotide, leaving a DNA fragment of a certain length, which can be sequenced on the machine. A polyacrylamide solution is first injected into a hollow capillary during the sequencing process. Then, the polyacrylamide solution was ionized by UV light irradiation to generate a polymerization reaction. The polyacrylamide gel produces a separation effect under the electric field to start the electrophoresis of nucleotide. The electrophoretic movement of short DNA fragments is fast, and the electrophoretic movement of long DNA fragments is slow. The mixture of DNA fragments moves from a negative charge to a positive charge under the action of an electric field in a capillary containing a polyacrylamide gel. The positive end of the capillary is irradiated with a solid-state laser, and a spectroscopic optical sensor records the different fluorescence intensities. Each DNA fragment, when passing through the laser scanning point, has a fluorescent group on it, which will emit a specific fluorescent color.
Because in the previous polymerization reaction process, the starting point of the polymerization reaction starts from a specific primer position. Therefore, the DNA fragment that reaches the laser scanning point of electrophoresis first is the shorter fragment, so its polymerization termination position will be closer to the polymerization start position. Therefore, the fluorescent color reflects which of the bases at its 3' end is A, T, C, and G.
Conversely, the slower the electrophoresis of DNA fragments reaches the laser scanning point, the longer the DNA fragments. As a result, its termination site is farther away from the starting position of the primer. Finally, a map of four colors is obtained.
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