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Post by GodFather on Oct 9, 2013 18:11:19 GMT 5.5
Inexpensive drug may minimize damage from heart attack
Early treatment of heart attack patients with an inexpensive beta-blocker drug called metoprolol, while in transit to the hospital, can significantly reduce damage to the heart during a myocardial infarction, according to clinical trial study results published in the journal Circulation. The study was a collaboration between Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) in Spain and Icahn School of Medicine at Mount Sinai in New York.
The study, involving emergency ambulances and seven hospitals across Spain, shows this simple, low-cost intervention strategy with metoprolol could be easily extended throughout the world, to provide significant clinical benefit and could change current treatment practice for heart attack patients. Currently, patients receive no medication before undergoing routine angioplasty, the standard treatment for removing a heart blockage that causes a heart attack and damages heart tissue.
Borja Ibáñez, MD, PhD, head of the Experimental Cardiology Group at CNIC and clinical cardiologist at the Hospital Clínico San Carlos in Spain, is the joint lead investigator of this novel study with Valentín Fuster, MD, PhD, General Director of CNIC, who also serves as Director of Mount Sinai Heart and Physician-in-Chief at The Mount Sinai Medical Center. Also, Dr. Fuster will begin his term in 2014 as the next Editor-in-Chief of the Journal of the American College of Cardiology (JACC).
Metoprolol, a drug of the beta-blocker family, has been available for more than 30 years to treat arterial hypertension and other cardiovascular conditions. In this new study, the team of researchers were able to examine the potential usefulness of metoprolol after a heart attack. The clinical trial named METOCARD-CNIC is the first to test metoprolol therapy, at a cost less than three dollars (or less than two euros), in heart attack patients undergoing standard angioplasty treatment procedures.
According to researchers, the potential savings from this medical therapy intervention may go far beyond the low cost of metoprolol itself, since patients experiencing less-extensively damaged heart muscle are less likely to need more costly treatments such as an implantable defibrillator or to require costly hospitalization for treatment of heart failure. Dr. Ibáñez explains, "the savings in healthcare costs will run into millions; a per-patient outlay of less than two euros (or less than three dollars) will over the years save thousands." Currently, researchers are now carrying out a cost-effectiveness analysis to give a firm estimate of the expected savings.
An acute myocardial infarction, or heart attack, is caused by a sudden obstruction of one of the coronary arteries. A blockage requires immediate medical attention and the response time is critical. With every minute that the artery is blocked, the cells of the heart die becoming necrotic, in exponentially growing numbers. According to researchers, the best strategy for limiting the size of an infarct is to carry out the angioplasty procedure as soon as possible. A delay in reopening the coronary artery could mean a larger region of damaged or necrotic tissue. When necrosis is extensive, the heart loses a large part of its pumping strength, which does not recover.
In addition to the high risk of death during the infarction, survivors are likely to suffer from heart failure and severe arrhythmias, and often may die in the months or years following the attack. "The larger the infarct (death of cardiac muscle), the greater the probability that survivors will suffer these complications in the future," says co-lead investigator Dr. Fuster, who also serves as Director of the Zena and Michael A. Wiener Cardiovascular Institute and the Marie-Josée and Henry R. Kravis Center for Cardiovascular Health at The Mount Sinai Medical Center.
Therefore, Dr. Fuster stresses reducing the amount of tissue that is damaged or dies during an infarction is of the utmost importance. Over the last several decades investigators have searched unsuccessfully for a complementary therapy that would further reduce the extent of heart damage.
A total of 270 patients with infarction were recruited since 2010 in four of Spain's regions including: Madrid, Galicia, León, and Cantabria. In the randomized study, patients were assigned to receive either intravenous metoprolol or a placebo treatment at the moment of diagnosis of a myocardial infarction during ambulance transit to the catheterization laboratory. Hospitals in Spain participating in the METOCARD-CNIC trial included: Hospital Clínico San Carlos, Hospital de La Princesa, Hospital 12 de Octubre, Hospital Puerta de Hierro, and Hospital Quirón (Madrid), Hospital Meixoeiro (Galicia), Hospital de León (León), and Hospital Marqués de Valdecilla (Cantabria).
The efficacy of the medical intervention was evaluated by magnetic resonance imaging (MRI) a week after the infarction. MRI measured the mass of damaged heart tissue in all patients. The results showed patients who received metoprolol had much smaller infarcts than those who received the control treatment, and that this smaller infarct size was linked to greater heart contractility.
"MRI is a unique tool for studying heart tissue that enables us to explore in exquisite detail heart function, necrosis, the state of the microcirculation, and many other parameters that are critical in determining the post-infarction status of the myocardium," says Dr. Fuster.
The MRI scans were analyzed at the central CNIC laboratory by cardiologists blinded to the treatment. The CNIC team of cardiologists are experts in this analysis, and most of them received their training from Dr. Fuster at The Mount Sinai Medical Center in New York through a bilateral training agreement with the CNIC.
Initial research investigations about the potential benefits of metoprolol were first launched at The Mount Sinai Medical Center in 2006 while Dr. Ibáñez was working there with Dr. Fuster and Mount Sinai's Juan Badimon, PhD, Director of the Atherothrombosis Research Unit at its Cardiovascular Institute. Their preclinical research findings about metoprolol in animal models, analyzed using MRI and published in the journal Circulation in 2007, showed early administration of metoprolol during heart attack increased myocardial salvage and led to the translational medicine potential for human clinical trial.
The research team is currently investigating the molecular mechanism underlying the therapeutic action of metoprolol. Antonio Fernández-Ortiz, MD, PhD, co-investigator on the METOCARD-CNIC study and leader of this sub-study, explains that "this project analyzes the effect of metoprolol on the interaction of blood platelets with inflammatory cells, which might explain the benefit of early treatment with this drug as soon as possible after diagnosis of a heart attack."
Researchers are planning to extend the clinical trial to a much larger number of patients in a multinational study, to demonstrate not only a reduced infarct size, but also a reduced mortality in patients who receive early metoprolol during transit to hospital. The CNIC research team, colleagues in the emergency services, and hospitals are already working on the logistics of a new international clinical trial.
In an editorial accompanying the published article in Circulation, experts from the Technische Universität and the Munich Heart Alliance, Gjin Ndrepepa and Adnan Kastrati, affirmed that, if confirmed by a subsequent analysis of large numbers of patients, the results of METOCARD-CNIC trial are likely to lead to a change in clinical practice: "In this regard, a pharmaco-protective strategy able to reduce infarct size by 20 percent when used in conjunction with primary PCI nurtures great hope in clinical benefit."
In addition, Dr. Ibáñez adds: "the professionals of the emergency ambulance services were the driving force of this study. Their hard work is a professional and human example to us all; we are deeply humbled by the readiness of so many professionals to commit themselves 24 hours a day, 365 days a year to an altruistic project."
Funding for this METOCARD-CNIC clinical trial study was received from the Spanish Ministry of Economy and Competitiveness, a competitive research grant from the CNIC, and the assignation of CNIC as a Severo Ochoa center in 2011. Additionally, support was received from the Spanish Ministry of Health, Social Services and Equality, Philips, the Fundación Mutua Madrileña, and from members of the Pro-CNIC Foundation, which manages private contributions to the CNIC.
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Post by GodFather on Oct 14, 2013 16:22:26 GMT 5.5
Compound in grapes, red wine could help treat multiple types of cancer
A recent study by a University of Missouri researcher shows that resveratrol, a compound found in grape skins and red wine, can make certain tumor cells more susceptible to radiation treatment. This research, which studied melanoma cells, follows a previous MU study that found similar results in the treatment of prostate cancer. The next step is for researchers to develop a successful method to deliver the compound to tumor sites and potentially treat many types of cancers.
"Our study investigated how resveratrol and radiotherapy inhibit the survival of melanoma cells," said Michael Nicholl, MD, assistant professor of surgery at the MU School of Medicine and surgical oncologist at Ellis Fischel Cancer Center in Columbia, Mo. "This work expands upon our previous success with resveratrol and radiation in prostate cancer. Because of difficulties involved in delivery of adequate amounts of resveratrol to melanoma tumors, the compound is probably not an effective treatment for advanced melanoma at this time."
The study found that melanoma cells become more susceptible to radiation if they were treated first with resveratrol. The MU researcher found that when the cancer was treated with resveratrol alone, 44 percent of the tumor cells were killed. When the cancer cells were treated with a combination of both resveratrol and radiation, 65 percent of the tumor cells died.
Nicholl said his findings could lead to more research into the cancer-fighting benefits of the naturally occurring compound.
"We've seen glimmers of possibilities, and it seems that resveratrol could potentially be very important in treating a variety of cancers," Nicholl said. "It comes down to how to administer the resveratrol. If we can develop a successful way to deliver the compound to tumor sites, resveratrol could potentially be used to treat many types of cancers. Melanoma is very tricky due to the nature of how the cancer cells travel throughout the body, but we envision resveratrol could be combined with radiation to treat symptomatic metastatic tumors, which can develop in the brain or bone."
Resveratrol supplements are available over the counter in many health food sections at grocery stores. Nicholl does not recommend that patients rely on resveratrol supplements to treat cancer because more research is needed.
Nicholl's study was published in the Journal of Surgical Research, the journal for the Association for Academic Surgery. If additional studies are successful within the next few years, MU officials will request authority from the federal government to begin human drug development. This is commonly referred to as the "investigative new drug" status. After this status has been granted, researchers may conduct clinical trials with the hope of developing new treatments for cancer.
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Post by GodFather on Oct 14, 2013 16:30:53 GMT 5.5
AstraZeneca enters co-promotion agreement with Janssen in Japan for innovative prostate cancer treatment
AstraZeneca today announced that it has entered into an agreement with Janssen Pharmaceuticals K. K. in Japan to co-promote abiraterone acetate, an innovative oral therapy for the treatment of patients with prostate cancer. Currently the main treatment option available to patients in Japan is medical castration, however prostate cancer can still progress in many patients because androgens are produced in other tissues. Abiraterone acetate, a CYP17-inhibitor, inhibits the key enzyme which modulates the production of androgens, hormones which stimulate prostate cancer cells to grow, from all sources in the body. This helps lower the level of androgens available to the prostate cancer cells, which is the goal of treatment in prostate cancer.
Janssen Pharmaceuticals K.K. submitted a marketing approval application for abiraterone acetate to the Japanese Ministry of Health, Labour and Welfare in July 2013 for the treatment of prostate cancer. The product was approved in the US by the Food and Drug Administration in April 2011, and in the EU by the European Commission in September 2011 for the treatment of patients with metastatic castration-resistant prostate cancer.
Marc Dunoyer, Executive Vice President, Global Products and Portfolio Strategy at AstraZeneca said: "Japan is one of the fastest growing pharmaceutical markets, where AstraZeneca has a proven track record of successfully developing and marketing innovative medicines. Abiraterone acetate is a great addition to our existing portfolio of leading cancer treatments, with real potential to address an important and growing patient need. This deal is a strong strategic fit for AstraZeneca, reinforcing both our focus on oncology as a core therapy area and Japan as one of our key growth drivers."
Financial terms of the agreement were not disclosed.
About abiraterone acetate
Abiraterone acetate is indicated in the US and the EU for the treatment of patients with metastatic castration-resistant prostate cancer in combination with prednisone (steroid) before and after treatment with docetaxel (chemotherapy). Abiraterone acetate has been approved in 83 countries.
About AstraZeneca
AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of cardiovascular, metabolic, respiratory, inflammation, autoimmune, oncology, infection and neuroscience diseases. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide.
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Post by GodFather on Oct 14, 2013 16:36:45 GMT 5.5
Stem cell breakthrough could set up future transplant therapies
A new method for creating stem cells for the human liver and pancreas, which could enable both cell types to be grown in sufficient quantities for clinical use, has been developed by scientists. Using the technique, researchers have for the first time been able to grow a pure, self-renewing population of stem cells specific to the human foregut, the upper section of the human digestive system.
These so-called "Foregut stem cells" could then be developed further to produce liver or pancreatic cells. The method significantly improves on existing techniques for cultivating this type of stem cell, and raises the possibility that, with further work, they could be grown in large numbers in bioreactors. That would make it possible to use them for regenerative therapies, repairing damaged organs or tissues in the body, and treating conditions such as type I diabetes or liver disease.
"We have developed a cell culture system which allows us to specifically isolate foregut stem cells in the lab," Dr Nicholas Hannan, from the University of Cambridge Wellcome Trust MRC Stem Cell Institute, Department of Surgery, explained. Hannan led the study, which was carried out in the lab of Dr Ludovic Vallier.
"These cells have huge implications for regenerative medicine, because they are the precursors to the thyroid upper airways, lungs, liver, pancreas, stomach and biliary systems. We now have a system where we may be able to create all these cell types from the same starting population."
As reported in the journal Stem Cell Reports, the method also means that researchers will be able to analyse the embryonic development of foregut cells in greater depth. "We now have a platform from which we can study the early patterning events that occur during human development to produce the intestines, liver, lungs and pancreas," Hannan added.
The approach marks a breakthrough because it overcomes some of the problems which currently limit scientists' abilities to grow cells associated with the liver, pancreas, and other parts of the foregut in sufficiently large numbers for clinical use.
Stem cell growth starts with human pluripotent stem cells (hPSCs). These are non-specialised biological cells with the potential to transform - or "differentiate" - into any of the three primary layers of cells from which all tissues and organs develop. Because these cells also self-renew, creating copies of themselves, they offer the potential to provide an infinite source of clinically usable cells for regenerative medicine.
Achieving this, however, relies on scientists developing effective methods through which they can influence the differentiation of hPSCs. To grow pancreatic or liver cells, hPSCs are differentiated into the endoderm - the primary tissue layer associated with the digestive and respiratory systems. This provides a base population of progenitors which researchers can then try to develop as more specialised cells.
Unfortunately, the approach is far from perfect. In particular, it is difficult to produce a pure population of the required progenitors, and "contaminating" cells of the wrong type are typically found within the cell culture. This makes it difficult to identify the target cells for further differentiation in the lab and can complicate the application of these cells in transplant therapies. In some cases, hPSCs also produce such a large number of contaminating cells that the precursor population becomes unusable.
To address these limitations, the research team carried out a detailed study of the conditions in which stem cells differentiate specifically into the human foregut - the section of the digestive system extending from the mouth to the duodenum, and including the liver and pancreas.
By manipulating the signal pathways of the cells, and varying the environment in which the cells were developed and the substrate on which they were grown, they were able to isolate the precise culture needed for the differentiation of cells associated with the foregut itself. When heavily contaminated stem cell populations were developed under these conditions, the contaminating, non-endodermal cells eventually stopped proliferating and gradually disappeared. The universal nature of this culture system takes a step towards a universal system that could be used to treat any patient requiring cells for transplantation purposes.
The result was a much purer, self-renewing population of human foregut stem cells (hFSCs). The cells generated are true stem cells because they are able to self renew and can differentiate towards any part of the foregut. Because they are also still at the stage where they self-renew, they could be grown in large enough numbers to be used in clinical therapies.
The team was also able to show that these human foregut stem cells do not form tumours, which means that they can be safely injected for therapeutic purposes, without having adverse side effects.
Although the procedure does not improve scientists' ability to produce pancreatic or liver cells specifically, it does provide a much purer source population for doing so. "What we have now is a better starting point - a sustainable platform for producing liver and pancreatic cells," Dr Ludovic Vallier said, senior author of the study. "It will improve the quality of the cells that we produce and it will allow us to produce the large number of uncontaminated cells we need for the clinical application of stem cell therapy."
The team is now building on the research by studying the fundamental mechanisms which control the differentiation of hFSCs specifically as liver cells or pancreatic cells, to further improve the production of these cell types for regenerative medicine.
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Post by GodFather on Oct 14, 2013 16:39:32 GMT 5.5
Stem cell breakthrough could set up future transplant therapies
A new method for creating stem cells for the human liver and pancreas, which could enable both cell types to be grown in sufficient quantities for clinical use, has been developed by scientists. Using the technique, researchers have for the first time been able to grow a pure, self-renewing population of stem cells specific to the human foregut, the upper section of the human digestive system.
These so-called "Foregut stem cells" could then be developed further to produce liver or pancreatic cells. The method significantly improves on existing techniques for cultivating this type of stem cell, and raises the possibility that, with further work, they could be grown in large numbers in bioreactors. That would make it possible to use them for regenerative therapies, repairing damaged organs or tissues in the body, and treating conditions such as type I diabetes or liver disease.
"We have developed a cell culture system which allows us to specifically isolate foregut stem cells in the lab," Dr Nicholas Hannan, from the University of Cambridge Wellcome Trust MRC Stem Cell Institute, Department of Surgery, explained. Hannan led the study, which was carried out in the lab of Dr Ludovic Vallier.
"These cells have huge implications for regenerative medicine, because they are the precursors to the thyroid upper airways, lungs, liver, pancreas, stomach and biliary systems. We now have a system where we may be able to create all these cell types from the same starting population."
As reported in the journal Stem Cell Reports, the method also means that researchers will be able to analyse the embryonic development of foregut cells in greater depth. "We now have a platform from which we can study the early patterning events that occur during human development to produce the intestines, liver, lungs and pancreas," Hannan added.
The approach marks a breakthrough because it overcomes some of the problems which currently limit scientists' abilities to grow cells associated with the liver, pancreas, and other parts of the foregut in sufficiently large numbers for clinical use.
Stem cell growth starts with human pluripotent stem cells (hPSCs). These are non-specialised biological cells with the potential to transform - or "differentiate" - into any of the three primary layers of cells from which all tissues and organs develop. Because these cells also self-renew, creating copies of themselves, they offer the potential to provide an infinite source of clinically usable cells for regenerative medicine.
Achieving this, however, relies on scientists developing effective methods through which they can influence the differentiation of hPSCs. To grow pancreatic or liver cells, hPSCs are differentiated into the endoderm - the primary tissue layer associated with the digestive and respiratory systems. This provides a base population of progenitors which researchers can then try to develop as more specialised cells.
Unfortunately, the approach is far from perfect. In particular, it is difficult to produce a pure population of the required progenitors, and "contaminating" cells of the wrong type are typically found within the cell culture. This makes it difficult to identify the target cells for further differentiation in the lab and can complicate the application of these cells in transplant therapies. In some cases, hPSCs also produce such a large number of contaminating cells that the precursor population becomes unusable.
To address these limitations, the research team carried out a detailed study of the conditions in which stem cells differentiate specifically into the human foregut - the section of the digestive system extending from the mouth to the duodenum, and including the liver and pancreas.
By manipulating the signal pathways of the cells, and varying the environment in which the cells were developed and the substrate on which they were grown, they were able to isolate the precise culture needed for the differentiation of cells associated with the foregut itself. When heavily contaminated stem cell populations were developed under these conditions, the contaminating, non-endodermal cells eventually stopped proliferating and gradually disappeared. The universal nature of this culture system takes a step towards a universal system that could be used to treat any patient requiring cells for transplantation purposes.
The result was a much purer, self-renewing population of human foregut stem cells (hFSCs). The cells generated are true stem cells because they are able to self renew and can differentiate towards any part of the foregut. Because they are also still at the stage where they self-renew, they could be grown in large enough numbers to be used in clinical therapies.
The team was also able to show that these human foregut stem cells do not form tumours, which means that they can be safely injected for therapeutic purposes, without having adverse side effects.
Although the procedure does not improve scientists' ability to produce pancreatic or liver cells specifically, it does provide a much purer source population for doing so. "What we have now is a better starting point - a sustainable platform for producing liver and pancreatic cells," Dr Ludovic Vallier said, senior author of the study. "It will improve the quality of the cells that we produce and it will allow us to produce the large number of uncontaminated cells we need for the clinical application of stem cell therapy."
The team is now building on the research by studying the fundamental mechanisms which control the differentiation of hFSCs specifically as liver cells or pancreatic cells, to further improve the production of these cell types for regenerative medicine.
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Post by GodFather on Oct 14, 2013 16:43:48 GMT 5.5
Novartis launches fully interactive Facebook ‘Retina App’ on World Sight Day to raise awareness of retinal disease
Today, Novartis further embraces the worldwide vision impairment community by supporting World Sight Day with the launch of a new Facebook 'Retina App'. The app simulates retinal disease by illustrating the user's journey by showing a highly realistic view of what the impact of vision loss on their daily life could look like. A part of the Set Your Sights campaign, the app will be launched alongside dedicated social media communities allowing people with low vision conditions and wider audiences to further engage and build a community of support.
This engaging campaign has been mounted in response to the World Health Organization's 2020 Vision Report which asserts that nearly 80% of global blindness is preventable if managed correctly(1) and encourages people to directly engage with vision-loss and experience what it means to live with a sight-diminishing condition. The Set Your Sights campaign is the latest addition to the Novartis portfolio to address the medical needs of people living with conditions affecting their sight.
"As the global leader in the field of retinal disease, Novartis is proud to support World Sight Day by creating further dialogue among people living with low vision conditions and the wider community, generating an environment of understanding and tolerance," said David Epstein, Head of the Pharmaceuticals Division of Novartis Pharma AG. "This is an important initiative in the pharmaceutical environment, reflecting our focus to always put the patient first. Novartis is leading the industry, not only with our medicines, but by boldly experimenting with new technologies to re-define how the pharmaceutical industry engages people with their health."
Retina diseases include conditions such as wet AMD, diabetic macular edema (DME), retinal vein occlusion (RVO) and choroidal neovascularization secondary to pathologic myopia (myopic CNV). Novartis is leading the way to help address these conditions; Lucentis® (ranibizumab), designed to save sight, has demonstrated transformational efficacy across its licensed indications. It is licensed in many countries for wet AMD, for visual impairment due to DME, macular edema secondary to branch- and central-RVO, and visual impairment due to myopic CNV.
Set Your Sights: This is an interactive online campaign which aims to support people with retinal disease and those who care for them, enabling patients and caregivers to reclaim their lives, gain confidence and find inspiration and motivation to seek treatment for a better, more fulfilled life.
The campaign launches with a Facebook application (the Retina App) on World Sight Day (10 October 2013), which provides an interactive journey aimed at driving global awareness around the symptoms of retinal disease and the need to seek treatment. Users of the application will be presented with a fully tailored, through the lens of their own photos and friends, video experience that shows a highly realistic view of what their life with retinal disease could be like.
The launch will be supported with social conversations on Facebook www.facebook.com/SetYourSights and Twitter www.twitter.com/YourSights, providing the retinal disease community with relevant information on life, their passions and the condition.
World Sight Day was created by Lions Clubs International and blindness prevention organizations worldwide in 1998 and is now driven by the World Health Organization and the International Agency for the Prevention of Blindness to raise global awareness of blindness and vision impairment as major international public health issues. It is observed on the second Thursday of October each year.
Novartis commitment to Ophthalmology
Novartis commitment to ophthalmology is further demonstrated by sponsorship of the "eXcellence in Ophthalmology Vision Award" (XOVA). XOVA is an annual award launched in 2010 that provides funding to support innovative, sustainable projects to non-profit initiatives that aim to reduce the burden of blindness. There have been 11 awards to date and the scope of projects from the 2012 applications included: improving eye care in children, reaching rural communities, providing training and education, building or expanding eye-care centers, and installing or improving technology.
About Lucentis® (ranibizumab)
Lucentis was designed to save sight and has demonstrated transformational efficacy with individualized dosing in its licensed indications. As an antibody fragment with a short systemic half-life, Lucentis was specifically designed, developed, formulated and licensed for ocular conditions, and is manufactured to the highest standards for intra-ocular use.
Lucentis is licensed in more than 100 countries, for the treatment of wet AMD, visual impairment due to DME and for visual impairment due to macular edema secondary to RVO, including both branch- and central-RVO. Also, Lucentis is licensed in more than 30 countries for the treatment of patients with visual impairment due to myopic CNV. In most countries, including those in Europe, Lucentis has an individualized treatment regimen with the goal of maximizing visual outcomes while minimizing under- or over-treating patients.
Lucentis has a well-established safety profile supported by 43 extensive sponsored clinical studies and real-world experience. Its safety profile has been well established in a clinical development program that enrolled more than 12,500 patients across indications and there is more than 1.7 million patient-treatment years of exposure since its launch in the United States in 2006.
Lucentis was developed by Genentech and Novartis. Genentech has the commercial rights to Lucentis in the United States. Novartis has exclusive rights in the rest of the world. Lucentis is a registered trademark of Genentech Inc.
About Novartis
Novartis provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, eye care, cost-saving generic pharmaceuticals, preventive vaccines and diagnostic tools, over-the-counter and animal health products. Novartis is the only global company with leading positions in these areas. In 2012, the Group achieved net sales of USD 56.7 billion, while R&D throughout the Group amounted to approximately USD 9.3 billion (USD 9.1 billion excluding impairment and amortization charges). Novartis Group companies employ approximately 131,000 full-time-equivalent associates and operate in more than 140 countries around the world.
1. World Health Organization (WHO) Prevention of blindness and deafness. www.who.int/pbd/en/ Last Accessed September 2013.
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Post by GodFather on Oct 16, 2013 0:06:07 GMT 5.5
Aging tumor cells may be an effective cancer treatment
Scientists at the University of Massachusetts Medical School have shown that diffuse large B-cell lymphoma (DLBCL) may be susceptible to treatment by re-activating the normal aging program in tumor cells so they can no longer divide. The study, published in Nature Communications, details a novel, tumor-suppressive role for the Smurf2 protein - which typically plays an "enforcer" role in cellular aging, also called senescence - in a subset of DLBCL. Identification of this novel function for Smurf2 provides a new therapeutic target for treating this cancer.
"Normally, this pathway is responsible for senescence and suppressing proliferation of B cells," said Hong Zhang, PhD, assistant professor of cell & developmental biology at UMMS and senior author of the study. "However, human DLBCL show low levels of Smurf2 expression; these low levels affect a pathway that encourages un-checked cell division and tumor growth. It's possible that restoration of Smurf2 expression may provide therapeutic benefits for patients and help encourage remission in difficult to treat cases."
Diffuse large B-cell lymphoma is the most common form of non-Hodgkin's lymphoma. An estimated 70,000 people living in the United States will be diagnosed with non-Hodgkin's lymphoma in 2013, accounting for 30 to 40 percent of all new diagnoses. Roughly 50 percent of those diagnosed will not respond to conventional treatment or will relapse within five years. Rachel Gerstein, PhD, associate professor of microbiology and physiological systems at UMMS, and co-author of the study, notes that "the average age at the time of diagnosis with DLBCL is mid-60s. Therefore, it's particularly exciting to connect a glitch in cellular aging within DLBCL to this cancer that preferentially affects the elderly."
A 2012 Cancer Research study by Drs. Zhang, Gerstein and colleagues found that mice deficient in Smurf2 gene expression developed spontaneous tumors, including B-cell lymphoma. To determine if a similar Smurf2 deficiency was connected to human DLBCL, and better understand the molecular pathway being disturbed, Zhang and colleagues initiated a new study to examine Smurf2 expression in patients with DLBCL. They found that a significant subset of these tumor samples showed a marked decrease in Smurf2 expression. Furthermore, lower levels of Smurf2 correlated to poor survival prognosis. Taken together, these findings indicate a strong role for Smurf2 in human DLBCL.
Closer examination by the study authors, including first author Charusheila Ramkumar, PhD, a doctoral student in the Graduate School of Biomedical Sciences at UMMS and now a postdoctoral fellow, revealed that Smurf2 is part of a complex pathway incorporating the transcriptional regulator YY1 and the regulatory gene c-Myc (also a well known oncogene). Together, these three proteins collaborate to regulate cell proliferation and division. However, in a subset of DLBCL patients this cycle has gone awry.
Tumor cells that showed decreased levels of Smurf2 expression also had increased levels of YY1 and c-Myc expression. These increased levels of YY1 and c-Myc caused cells, including B-cells, to continue dividing. Unrestrained cell proliferation is a hallmark of many cancers and in the case of DLBCL cells with a perturbed Smurf2-YY1-c-Myc pathway, it leads to tumor formation.
Not only does the lack of Smurf2 lead to increased cell division through this pathway but it also allows the tumor cells to continue dividing longer. Because Smurf2 (which normally plays a part in cellular aging) expression levels are already low in DLBCL cells, these tumor cells don't age normally. As a result, tumor B-cells effectively remain younger longer, allowing them to proliferate even more.
"This enhanced cell proliferation induced by YY1 and c-Myc activation, coupled with impaired senescence due to low Smurf2 levels helps drive lymphoma formation," said Zhang. "It also suggests multiple roles for Smurf2 in tumor suppression in the form of suppressed cell proliferation and senescence response."
To gauge the potential clinical relevance of this basic biological discovery, Zhang and colleagues restored Smurf2 expression in human DLBCL cells. Once restored, proliferation of these cells was inhibited, providing new hope that therapeutics designed to increase expression of Smurf2 in lymphomas, when coupled with existing treatments, will be a more effective approach to achieving remission in patients.
The next step for Zhang and colleagues is to screen for molecules that can either increase or mimic the expression of Smurf2. He will also screen other cancer types, such as liver cancer, for the Smurf2-YY1-c-Myc pathway to see if they are also susceptible to this approach.
"This is another example of a basic biological discovery having important clinical applications," said Zhang. "When we started this line of inquiry we were interested in the role of Smurf2 in cellular aging. We never expected the clinical relevance to be so immediate and striking."
About the University of Massachusetts Medical School
The University of Massachusetts Medical School (UMMS), one of five campuses of the University system, is comprised of the School of Medicine, the Graduate School of Biomedical Sciences, the Graduate School of Nursing, a thriving research enterprise and an innovative public service initiative, Commonwealth Medicine. Its mission is to advance the health of the people of the Commonwealth through pioneering education, research, public service and health care delivery with its clinical partner, UMass Memorial Health Care. In doing so, it has built a reputation as a world-class research institution and as a leader in primary care education. The Medical School attracts more than $240 million annually in research funding, placing it among the top 50 medical schools in the nation. In 2006, UMMS's Craig C. Mello, PhD, Howard Hughes Medical Institute Investigator and the Blais University Chair in Molecular Medicine, was awarded the Nobel Prize in Physiology or Medicine, along with colleague Andrew Z. Fire, PhD, of Stanford University, for their discoveries related to RNA interference (RNAi). The 2013 opening of the Albert Sherman Center ushered in a new era of biomedical research and education on campus. Designed to maximize collaboration across fields, the Sherman Center is home to scientists pursuing novel research in emerging scientific fields with the goal of translating new discoveries into innovative therapies for human diseases.
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Post by GodFather on Oct 16, 2013 18:04:46 GMT 5.5
Drug activates virus against cancer
Parvoviruses cause no harm in humans, but they can attack and kill cancer cells. Since 1992, scientists at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have been studying these viruses with the aim of developing a viral therapy to treat glioblastomas, a type of aggressively growing brain cancer. A clinical trial has been conducted since 2011 at the Heidelberg University Neurosurgery Hospital to test the safety of treating cancer patients with the parvovirus H-1.
"We obtained impressive results in preclinical trials with parvovirus H-1 in brain tumors," says Dr. Antonio Marchini, a virologist at DKFZ. "However, the oncolytic effect of the viruses is weaker in other cancers. Therefore, we are searching for ways to increase the therapeutic potential of the viruses."
In doing so, the virologists also tested valproic acid, a drug belonging to a group of drugs called HDAC inhibitors. The effect of these inhibitors is to raise the transcription of many genes that have been chemically silenced. Valproic acid is commonly used to treat epilepsy and has also proven effective in treating specific types of cancer.
The researchers initially used a combination of parvoviruses and valproic acid to treat tumor cells that had been obtained from cervical and pancreatic carcinomas and raised in the culture dish. In both types of cancer, the drug raised the rate of virus-induced cell death; in some cases, the cancer cells were even completely eliminated.
The encouraging results obtained in cultured cells were confirmed in cervical and pancreatic tumors that had been transplanted to rats. After the animals were treated with a combination of parvoviruses and valproic acid, in some cases the tumors regressed completely and animals remained free of recurrences over a one-year period. In contrast, animals treated with the same virus dose without the drug displayed no regression, not even when a 20-times higher dose of viruses was administered.
The virologists were also able to unravel the molecular mechanism by which valproic acid assists parvoviruses in fighting cancer: Treatment with the drug activates a viral protein called NS1, which is toxic. This helps the viruses replicate more rapidly and kill cancer cells more effectively.
The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 2,500 employees is the largest biomedical research institute in Germany. At DKFZ, more than 1,000 scientists investigate how cancer develops, identify cancer risk factors and endeavor to find new strategies to prevent people from getting cancer. They develop novel approaches to make tumor diagnosis more precise and treatment of cancer patients more successful. The staff of the Cancer Information Service (KID) offers information about the widespread disease of cancer for patients, their families, and the general public. Jointly with Heidelberg University Hospital, DKFZ has established the National Center for Tumor Diseases (NCT) Heidelberg, where promising approaches from cancer research are translated into the clinic. In the German Consortium for Translational Cancer Research (DKTK), one of six German Centers for Health Research, DKFZ maintains translational centers at seven university partnering sites. Combining excellent university hospitals with high-profile research at a Helmholtz Center is an important contribution to improving the chances of cancer patients. DKFZ is a member of the Helmholtz Association of National Research Centers, with ninety percent of its funding coming from the German Federal Ministry of Education and Research and the remaining ten percent from the State of Baden-Württemberg.
"The synergistic effect of a combination of parvoviruses and valproic acid enables us to deliver both the viruses and the drug at low doses, which prevents severe side effects," Marchini explains. "The results are encouraging us to carry out further tests of this combination therapy. We believe it has the potential to arrest tumor growth in severe cases of cancer."
Junwei Li, Serena Bonifati, Georgi Hristov, Tiina Marttila, Severine Valmary-Degano,Sven Stanzel, Martina Schnölzer, Christiane Mougin, Marc Aprahamian, Svitlana P. Grekova, Zahari Raykov, Jean Rommelaere and Antonio Marchini: Synergistic combination of valproic acid and oncolytic parvovirus H-1PV as a potential therapy against cervical and pancreatic carcinomas. EMBO Molecular Medicine 2013, DOI: 10.1002/emmm.201302796
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Post by GodFather on Oct 16, 2013 18:06:49 GMT 5.5
AstraZeneca oncology portfolio strengthened as MedImmune acquisition of Spirogen boosts antibody-drug conjugate capability
AstraZeneca today announced that MedImmune, its global biologics research and development arm, has acquired Spirogen, a privately-held biotech company focused on antibody-drug conjugate technology for use in oncology. MedImmune has also entered into a collaboration agreement with ADC Therapeutics to jointly develop two of ADC Therapeutics' antibody-drug conjugate programmes in preclinical development. MedImmune will also make an equity investment in ADC Therapeutics, which has an existing licensing agreement with Spirogen.
MedImmune will acquire 100 per cent of Spirogen’s shares for an initial consideration of $200 million and deferred consideration of up to $240 million based on reaching predetermined development milestones. Existing out-licensing agreements and associated revenue streams are excluded from this acquisition.
MedImmune will also pay $20 million for an equity investment in ADC Therapeutics, which will be matched by Auven Therapeutics, the majority shareholder in both ADC Therapeutics and Spirogen. The collaboration agreement will include an upfront payment with predetermined development milestones for two programmes from a defined list and a cost- and profit-sharing arrangement with MedImmune representing the majority share. ADC Therapeutics will also have the option to co-promote one of the products in the US.
Antibody-drug conjugates are a clinically-validated cancer drug technology that offers both high potency and selective targeting of cancer cells. Spirogen's proprietary pyrrolobenzodiazepine (PBD) technology attaches highly potent cytotoxic agents, or ‘warheads’ to specific cancer-targeting antibodies using biodegradable 'linkers'. This targeting optimises the delivery of the cancer drug to the tumour cells only and provides the greatest degree of tumour killing while minimising the toxicity to the patient.
"Antibody-drug conjugates are ground-breaking technologies with the potential for directly targeting many types of cancer tumours while safeguarding healthy cells. The cutting-edge technologies developed by Spirogen and ADC Therapeutics complement MedImmune's innovative antibody engineering capabilities, enabling us to accelerate antibody-drug conjugates into the clinic," said Dr. Bahija Jallal, Executive Vice President, MedImmune.
Oncology is a core therapy area for AstraZeneca spanning both small molecule and biologics research and development. MedImmune is developing a comprehensive portfolio with an emphasis on two key areas in oncology development: antibody-drug conjugates and immune-mediated cancer therapy, which aims to harness the power of the patient's own immune system to fight cancer. Together, immune-mediated cancer therapies and antibody-drug conjugates have the potential to treat cancer in a way that current therapies are unable to do.
"This deal reflects the very significant progress made by our scientists, most notably over the last two years, as we have applied our warhead and linker technologies to the development of highly potent and specific antibody-drug conjugates," said Dr. Chris Martin, Chief Executive Officer, Spirogen. "We believe that pyrrolobenzodiazepine-armed antibody-drug conjugates will emerge as a critical component in the next generation of cancer biologics with the potential to make a difference for oncologists and their patients. We look forward to combining our world-class capabilities in this area with MedImmune’s ability to develop this exciting class of oncology drugs."
About Antibody-Drug Conjugates
An antibody-drug conjugate is a three-component system consisting of a potent cytotoxic agent, or 'warhead', a biodegradable linker and a monoclonal antibody. The antibody binds to specific markers at the surface of the cancer cell. The whole antibody-drug conjugate is then internalised within the cancer cell where the active drug is released. Antibody-drug conjugates have extensive potential therapeutic applications in several disease areas, particularly in cancer. The principle can also be applied beyond antibodies, with the possibility of linking warheads to antibody fragments, peptides, vitamins and hormones.
About Spirogen
The Spirogen group was founded in 2001 as a spin-out from several institutions including University College London and with partial funding by Cancer Research UK. It is majority owned by Auven Therapeutics. It has developed a novel class of highly potent cytotoxic warheads based on its proprietary pyrrolobenzodiazepines (PBDs), DNA minor groove binding agents, which bind and cross-link specific sites of DNA of the cancer cell. This blocks the cancer cells' division without distorting its DNA helix, thus potentially avoiding the common phenomenon of emergent drug resistance. Spirogen has been developing its PBD technology for more than ten years, including a standalone PBD agent in a Phase II study in acute myeloid leukemia. Its business model has been to partner its technology with pharma and biotech for use in the development of novel drugs. It has a number of industry collaborations, including collaborations with Genentech announced in 2011 and with ADC Therapeutics announced in 2012.
About ADC Therapeutics
ADC Therapeutics (ADCT) is a Swiss-based oncology drug development company that specialises in the development of proprietary antibody-drug conjugates (ADCs) targeting major cancers such as breast, lung, prostate, renal and blood. The company’s ADCs are highly targeted drug constructs which combine monoclonal antibodies specific to particular types of tumour cells with a novel class of highly potent PBD-based warheads. The company was launched in 2012 with a $50m commitment from private equity firm Auven Therapeutics. ADCT has access to warhead and linker chemistries via existing agreements with Spirogen. It operates a virtual business model based in Lausanne, Switzerland.
About Auven Therapeutics
Auven Therapeutics was founded by Stephen Evans-Freke and Dr. Peter B Corr in 2007 with an innovative investment strategy that enables it to operate as a drug development company while remaining structured as a private equity fund. Auven Therapeutics has a portfolio of biologic and small molecule drug candidates for a range of therapeutic indications including cancer, ophthalmic conditions, women’s health and orphan diseases. Auven manages its drug development activities from its bases in Lausanne, Switzerland, New York, USA and Hamilton, Bermuda. Auven Therapeutics Management LLLP, based in the US Virgin Islands, serves as its Investment Advisor.
About MedImmune
MedImmune is the worldwide biologics research and development arm of AstraZeneca. MedImmune is pioneering innovative research and exploring novel pathways across key therapeutic areas, including respiratory, inflammation and autoimmunity; cardiovascular and metabolic disease; oncology; neuroscience, and infection and vaccines. The MedImmune headquarters is located in Gaithersburg, MD, one of AstraZeneca's three global R&D centres.
About AstraZeneca
AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of cardiovascular, metabolic, respiratory, inflammation, autoimmune, oncology, infection and neuroscience diseases. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide.
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Post by GodFather on Oct 18, 2013 16:31:00 GMT 5.5
Statin, osteoporosis drug combo may help treat parasitic infections
Researchers at the University of Georgia have discovered that a combination of two commonly prescribed drugs used to treat high cholesterol and osteoporosis may serve as the foundation of a new treatment for toxoplasmosis, a parasitic infection caused by the protozoan Toxoplasma gondii. They published their findings recently in PLOS Pathogens.
Toxoplasma gondii is a parasite capable of infecting nearly all warm-blooded animals. While healthy human adults usually suffer no lasting ill effects from infection, it can be harmful or fatal to unborn fetuses or those with weakened immune systems.
"For many years, therapies for toxoplasmosis have focused on drugs that target only the parasite," said Silvia Moreno, senior author of the article and professor of cellular biology in UGA's Franklin College of Arts and Sciences. "But in this paper, we show how we can hit the parasite with two drugs simultaneously, one that affects body chemistry in the host and one that affects the parasite."
The UGA researchers discovered that a combination of the cholesterol lowering drug atorvastatin and osteoporosis medication zoledronic acid, both more commonly known by their respective trade names, Lipitor and Zometa, produce changes in the mammalian host and in the parasite that ultimately block parasite replication and spread of the infection.
"These two drugs have a strong synergy," said Moreno, who is also a member of UGA's Center for Tropical and Emerging Global Diseases. "The mice we treated were cured from a lethal infection using this combination approach."
Moreno and her colleagues began working on this drug combination following a series of experiments with unexpected results. They created a genetically modified version of the parasite in the laboratory that lacked a specific enzyme essential for one of the organism's most basic functions.
They thought such an experiment was an excellent opportunity to observe how the absence of this enzyme would kill the parasites. But every time they checked on the supposedly defective parasites, they were healthy and appeared completely unaffected.
"We kept asking ourselves, 'How did this happen? This enzyme should be essential to the parasite's survival,'" said Zhu-Hong Li, a UGA research scientist and lead author of the article. "It's almost like a human surviving without food or air."
What they discovered is that in order to survive, Toxoplasma has evolved an extraordinary ability to siphon essential compounds from its host when it is unable to make them on its own. This led them to the two-drug therapy.
Zoledronic acid prevents synthesis in the parasite and atorvastatin inhibits production in the host.
When Toxoplasma cannot produce these important molecules itself or steal them from its host, the parasites die.
"These drugs have been studied extensively, they are FDA-approved and safe for most people," Moreno said. "Plus, one might not have to take the drugs for an extended period, just long enough to clear the infection."
Moreno cautions that more research must be done before this becomes an accepted treatment for humans, but she hopes that a similar strategy might work for other serious parasitic diseases, such as malaria and cryptosporidiosis.
Early experiments with an anti-malarial drug already suggest that combining atorvastatin with fosmidomycin, an antibiotic effective against malaria parasites, creates a more potent antimalarial cocktail and it may lessen the risk of drug resistance.
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