The U.S. Food and Drug Administration today approved generic versions of the blood thinning drug Plavix (clopidogrel bisulfate), which helps reduce the risk of heart attack and stroke by making it less likely that platelets in the blood will clump and form clots in the arteries.
Clopidogrel is FDA-approved to treat patients who have had a recent heart attack or a recent stroke, or have partial or total blockage of an artery (peripheral artery disease).
“For people who must manage chronic health conditions, having effective and affordable treatment options is important,” said Keith Webber, Ph.D., deputy director of the Office of Pharmaceutical Science in the FDA’s Center for Drug Evaluation and Research. “The generic products approved today will expand those options for patients.”
Clopidogrel has a boxed warning to alert health care professionals and patients that the drug may not work well for those with certain genetic factors that affect how the body metabolizes the drug. Patients can be tested for these genetic factors to ensure that clopidogrel is the right choice for them. Also, certain medicines, such as proton pump inhibitors Prilosec (omeprazole) and Nexium (esomeprazole), reduce the effect of clopidogrel, leaving a person at greater risk for heart attack and stroke.
Clopidogrel may cause bleeding, which can be serious and sometimes lead to death. While taking the drug, people may bruise and bleed more easily, be more likely to have nose bleeds, and it may take longer for all bleeding to stop. Clopidogrel is dispensed with a patient Medication Guide that provides important instructions on its use and drug safety information.
Dr. Reddy's Laboratories, Gate Pharmaceuticals, Mylan Pharmaceuticals, and Teva Pharmaceuticals have gained FDA approval for 300 milligram (mg) clopidogrel. Apotex Corporation, Aurobindo Pharma, Mylan Pharmaceuticals, Roxane Laboratories, Sun Pharma, Teva Pharmaceuticals, and Torrent Pharmaceuticals have received approval for 75 mg clopidogrel.
Generic drugs approved by FDA are of the same high quality and strength as brand-name drugs. The generic manufacturing and packaging sites must pass the same quality standards as those for brand-name drugs.
Information about the availability of generic clopidogrel can be obtained from the manufacturers.
Tobacco is public health enemy number one. It kills six million people every year. The tobacco industry does everything it can to undermine anti-tobacco work. WHO has chosen "Stop tobacco industry interference" as the theme for the 2012 World No Tobacco Day - on 31 May. Discover the subversive methods of the tobacco industry by watching the campaign video. Find out what WHO, governments and civil society are doing, and how you can help stop the tobacco industry in its tracks, by joining the conversation on Twitter @WHO - #NoTobacco. (http://twitter.com/#!/who)
DIA 2012 is the premier global event that brings together more than 8,000 global professionals who are involved in every aspect of the discovery, development, and life cycle management of pharmaceuticals, biotechnology, medical devices, and related products.
The release of pseudo-generics or ‘fake’ generic drugs is common practice in Canada. This allows drug developers to maintain market share over a niche market of drug consumers, but also challenges generic companies’ ability to compete in the industry.
According to Health Canada Regulations, generic drugs have the same active pharmaceutical ingredients (APIs) and therapeutic effects as the corresponding brand name drugs, and differ only in their non-medicinal ingredients (aka excipients). Generic drugs sell at a fraction of the price of brand name drugs because they do not bear the extreme financial burden of extensive research and development phases, clinical trials, and brand marketing.
Generic drugs were first implemented following the Hatch-Waxman Act in 1984 which allowed generic drug manufactures to produce drug products with less fear of litigation from the drug’s innovators. This can only take place after the drug patent for the active ingredients has expired. Since the drug development process can take over 15 years from the original idea to the final drug product, drugs that have been approved by Health Canada and the FDA are awarded a 20 year patent that provides the manufacturer exclusive rights to sell the drug. This gives the innovator time to have sole marketing rights to their product, referred to as market exclusivity, and hopefully make back some of the money they have spent over the phases of research and development before other companies can enter the market with a generic version. When a drug patent expires all other companies are free to produce their own generic versions.
Patents can be extended when new uses for the drug are presented. Drug companies often scramble to find such indications so that they can extend their patent life and as a result be the sole providers of the drug for a longer amount of time. Competing companies similarly move quickly to release generic versions of drugs with closing patents in order capitalize on consumers looking for generic alternatives. In another attempt to maintain their market exclusivity, manufacturers of the brand name drug will release pseudo-generics which are identical to the brand name drug and manufactured on the same production line, but marketed and sold under a different name. Basically it is a ‘generic drug’ that is being produced by the brand name company.
This way, manufacturers can move quickly to infiltrate the generic drug market with little to no competition before the actual generic companies even have time to produce their products. This is beneficial for consumers who can get the same drug for 20-90% of its original cost. On the other hand, it is discouraging for competing generic companies because the market is already saturated with both the brand name drug and the pseudo-generic drugs, both made by the same company.
As a result there is a divide between innovation and competition. Innovator drug companies strive to maintain their market share and recoup costs associated with the development process; and generic companies fight to remain competitive in the industry.
Credits: Saaqshi Sharma Canadian Centre for Clinical Trials
NIH-funded study shows progress in brain-computer interface technology
In an ongoing clinical trial, a paralyzed woman was able to reach for and sip from a drink on her own – for the first time in nearly 15 years – by using her thoughts to direct a robotic arm. The trial, funded in part by the National Institutes of Health, is evaluating the safety and feasibility of an investigational device called the BrainGate neural interface system. This is a type of brain-computer interface (BCI) intended to put robotics and other assistive technology under the brain's control.
A report published today in Nature describes how two individuals — both paralyzed by stroke — learned to use the BrainGate system to make reach-and-grasp movements with a robotic arm, as part of the BrainGate2 clinical trial. The report highlights the potential for long-term use and durability of the BrainGate system, part of which is implanted in the brain to capture the signals underlying intentional movement. It also describes the most complex functions to date that anyone has been able to perform using a BCI.
For the woman, it was the first time since her stroke that she was able to sip a drink without help from a caregiver.
"The smile on her face was a remarkable thing to see. For all of us involved, we were encouraged that the research is making the kind of progress that we had all hoped," said the trial's lead investigator, Leigh Hochberg, M.D., Ph.D., who is an associate professor of engineering at Brown University in Providence, R.I. and a critical care neurologist at Massachusetts General Hospital (MGH)/Harvard Medical School in Boston.
"Years after the onset of paralysis, we found that it was still possible to record brain signals that carry multi-dimensional information about movement and that those signals could be used to move an external device," Dr. Hochberg said.
He noted that the technology is years away from practical use and that the trial participants used the BrainGate system under controlled conditions in their homes with a technician present to calibrate it.
The BrainGate neural interface system consists of a sensor to monitor brain signals and computer software and hardware that turns these signals into digital commands for external devices. The sensor is a baby aspirin-sized square of silicon containing 100 hair-thin electrodes, which can record the activity of small groups of brain cells. It is implanted into the motor cortex, a part of the brain that directs movement.
"This technology was made possible by decades of investment and research into how the brain controls movement. It’s been thrilling to see the technology evolve from studies of basic neurophysiology and move into clinical trials, where it is showing significant promise for people with brain injuries and disorders," said Story Landis, Ph.D., director of NIH's National Institute of Neurological Disorders and Stroke (NINDS). The institute funds BCI research in hopes of restoring function and improving quality of life for people coping with limb amputations or paralysis from spinal cord injury, stroke or neuromuscular disorders.
NIH has supported basic and applied research in this area for more than 30 years. In 2009 and 2010, an additional $3.8 million in NIH funding was made possible through the Recovery Act.
The latest analysis from the BrainGate2 trial focused on two participants — a 58-year-old woman and a 66-year-old man. Both individuals are unable to speak or move their limbs because of brainstem strokes they had years ago — the woman's in 1996 and the man's in 2006. In the trial, both participants learned to perform complex tasks with a robotic arm by imagining the movements of their own arms and hands.
In one task, several foam targets were mounted on levers on a tabletop and programmed to pop up one at a time, at different positions and heights. The participants had less than 30 seconds to grasp each target using the DEKA Arm System (Generation 2), which is designed to work as a prosthetic limb for people with arm amputations. One participant was able to grasp the targets 62 percent of the time, and the other had a 46 percent success rate.
This YouTube video describes how two trial participants were able to use the BrainGate system to make complex reach-and-grasp movements with a robotic arm, simply by imagining they were using their own arms. Credit: The BrainGate Collaboration.
In some sessions, the woman controlled a DLR Light-Weight Robot III arm, which is heavier than the DEKA arm and designed to be used as an external assistive device. She used this arm prior to the DEKA arm in the foam target task, and had a success rate of 21 percent. In other sessions with the DLR arm, her task was to reach for a bottled drink, bring it to her mouth and sip from a straw. She was able to complete four out of six attempts.
This is not the first glimmer of hope from human BCI research. Participants in the BrainGate trial and other studies have also used BCI technology to perform point-and-click actions with a computer cursor, a level of control that has been used for communication.
"This is another big jump forward to control the movements of a robotic arm in three-dimensional space. We’re getting closer to restoring some level of everyday function to people with limb paralysis," said John Donoghue, Ph.D., who leads the development of BrainGate technology and is the director of the Institute for Brain Science at Brown University.
Dr. Donoghue said the woman's ability to use the BrainGate was especially encouraging because her stroke occurred nearly 15 years ago and her sensor was implanted more than five years ago. Some researchers have wondered whether neurons in the motor cortex might die or stop generating meaningful signals after years of disuse. Researchers in the field have also worried that years after implantation, the sensor might break down and become less effective at enabling complex motor functions.
Roderic Pettigrew, M.D., Ph.D., director of NIH's National Institute of Biomedical Imaging and Bioengineering (NIBIB), which supports the research, indicated that the technology is promising, but at present is still undergoing development and evaluation. "The researchers have begun the long, difficult process of testing and refining the system with feedback from patients, and they've found that it is possible for a person to mentally control a robotic limb in three-dimensional space. This represents a remarkable advance," he said.
As the trial continues, the BrainGate research team needs to test the technology in more individuals, they said. They envision a system that would be stable for decades, wireless and fully automated. For now, the sensor — and therefore the user — must be connected via cables to the rest of the system. Prior to each session with the robotic arms, a technician had to perform a calibration procedure that lasted 31 minutes on average. Improvements are also needed to enhance the precision and speed of control. In the foam target task, for example, a successful reach-and-grasp motion typically took almost 10 seconds.
The ultimate goal for helping people with paralysis is to reconnect the brain directly to paralyzed limbs rather than robotic ones, the researchers said. In the future, the BrainGate system might be used to control a functional electrical stimulation (FES) device, which delivers electrical stimulation to paralyzed muscles. Such technology has shown promise in monkeys. The Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD) has long supported the clinical trial research for BrainGate, with the goal of enabling mental control of an FES system for limb movement. In previous reports from the BrainGate2 trial, a participant was able to use the BrainGate system to direct the movements of a virtual, computer-animated arm designed to simulate FES control of a real arm.
To support this research, NIH has worked closely with the Department of Veterans Affairs (VA) and the Defense Advanced Research Projects Agency (DARPA), the research arm of the Department of Defense. DARPA supports development of the DEKA arm. Development of the DLR arm is funded by the German aerospace agency DLR. NIH has supported the fundamental neuroscience and BCI development, and the clinical research in collaboration with the VA. Drs. Hochberg and Donoghue hold research positions with the Providence VA Medical Center.
Dr. Donoghue is supported by a Javits Neuroscience Investigator award (NS025074) from NINDS, and by a grant (EB007401) from NIBIB and NICHD. The research is also supported by contracts (HD53403, HD100018) from NICHD's National Center for Medical Rehabilitation Research to Robert Kirsch, Ph.D., at Case Western Reserve University, Cleveland. Additional support came from an NIH Challenge grant (HD063931) to Dr. Donoghue and a grant (DC009899) from the National Institute on Deafness and other Communication Disorders (NIDCD) to Dr. Hochberg, which were funded all or in part through the Recovery Act.
The BrainGate trial began in 2004 and was run by Cyberkinetics Inc., in collaboration with Brown University and MGH. NICHD began funding the trial in 2005. After Cyberkinetics withdrew from the research for financial reasons, funding continued through this NICHD contract, MGH became the clinical trial and administrative lead, and the trial was renamed BrainGate2. The trial is currently recruiting. For more information, visit:http://www.clinicaltrials.gov/ct2/show/NCT00912041 or http://www.braingate2.org.
NIBIB (http://www.nibib.nih.gov) is dedicated to improving health by bridging the physical and biological sciences to develop and apply new biomedical technologies.
NICHD (http://www.nichd.nih.gov) sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation.
NIDCD (http://www.nidcd.nih.gov) supports and conducts research and research training on the normal and disordered processes of hearing, balance, taste, smell, voice, speech and language and provides health information, based upon scientific discovery, to the public.
NINDS (http://www.ninds.nih.gov) is the nation's leading funder of research on the brain and nervous system. The NINDS mission is to reduce the burden of neurological disease — a burden borne by every age group, by every segment of society, by people all over the world.
Older adults who drank coffee — caffeinated or decaffeinated — had a lower risk of death overall than others who did not drink coffee, according a study by researchers from the National Cancer Institute (NCI), part of the National Institutes of Health, and AARP.
Coffee drinkers were less likely to die from heart disease, respiratory disease, stroke, injuries and accidents, diabetes, and infections, although the association was not seen for cancer. These results from a large study of older adults were observed after adjustment for the effects of other risk factors on mortality, such as smoking and alcohol consumption. Researchers caution, however, that they can't be sure whether these associations mean that drinking coffee actually makes people live longer. The results of the study were published in the May 17, 2012 edition of the New England Journal of Medicine.
Neal Freedman, Ph.D., Division of Cancer Epidemiology and Genetics, NCI, and his colleagues examined the association between coffee drinking and risk of death in 400,000 U.S. men and women ages 50 to 71 who participated in the NIH-AARP Diet and Health Study. Information about coffee intake was collected once by questionnaire at study entry in 1995-1996. The participants were followed until the date they died or Dec. 31, 2008, whichever came first.
The researchers found that the association between coffee and reduction in risk of death increased with the amount of coffee consumed. Relative to men and women who did not drink coffee, those who consumed three or more cups of coffee per day had approximately a 10 percent lower risk of death. Coffee drinking was not associated with cancer mortality among women, but there was a slight and only marginally statistically significant association of heavier coffee intake with increased risk of cancer death among men.
"Coffee is one of the most widely consumed beverages in America, but the association between coffee consumption and risk of death has been unclear. We found coffee consumption to be associated with lower risk of death overall, and of death from a number of different causes," said Freedman. "Although we cannot infer a causal relationship between coffee drinking and lower risk of death, we believe these results do provide some reassurance that coffee drinking does not adversely affect health."
The investigators caution that coffee intake was assessed by self-report at a single time point and therefore might not reflect long-term patterns of intake. Also, information was not available on how the coffee was prepared (espresso, boiled, filtered, etc.); the researchers consider it possible that preparation methods may affect the levels of any protective components in coffee.
"The mechanism by which coffee protects against risk of death — if indeed the finding reflects a causal relationship — is not clear, because coffee contains more than 1,000 compounds that might potentially affect health," said Freedman. "The most studied compound is caffeine, although our findings were similar in those who reported the majority of their coffee intake to be caffeinated or decaffeinated."
The National Cancer Institute (NCI) leads the National Cancer Program and the NIH effort to dramatically reduce the burden of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI Web site at http://www.cancer.gov or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).
The U.S. Food and Drug Administration today approved generic versions of the blood thinning drug Plavix (clopidogrel bisulfate), which helps reduce the risk of heart attack and stroke by making it less likely that platelets in the blood will clump and form clots in the arteries.
Clopidogrel is FDA-approved to treat patients who have had a recent heart attack or a recent stroke, or have partial or total blockage of an artery (peripheral artery disease).
“For people who must manage chronic health conditions, having effective and affordable treatment options is important,” said Keith Webber, Ph.D., deputy director of the Office of Pharmaceutical Science in the FDA’s Center for Drug Evaluation and Research. “The generic products approved today will expand those options for patients.”
Clopidogrel has a boxed warning to alert health care professionals and patients that the drug may not work well for those with certain genetic factors that affect how the body metabolizes the drug. Patients can be tested for these genetic factors to ensure that clopidogrel is the right choice for them. Also, certain medicines, such as proton pump inhibitors Prilosec (omeprazole) and Nexium (esomeprazole), reduce the effect of clopidogrel, leaving a person at greater risk for heart attack and stroke.
Clopidogrel may cause bleeding, which can be serious and sometimes lead to death. While taking the drug, people may bruise and bleed more easily, be more likely to have nose bleeds, and it may take longer for all bleeding to stop. Clopidogrel is dispensed with a patient Medication Guide that provides important instructions on its use and drug safety information.
Dr. Reddy's Laboratories, Gate Pharmaceuticals, Mylan Pharmaceuticals, and Teva Pharmaceuticals have gained FDA approval for 300 milligram (mg) clopidogrel. Apotex Corporation, Aurobindo Pharma, Mylan Pharmaceuticals, Roxane Laboratories, Sun Pharma, Teva Pharmaceuticals, and Torrent Pharmaceuticals have received approval for 75 mg clopidogrel.
Generic drugs approved by FDA are of the same high quality and strength as brand-name drugs. The generic manufacturing and packaging sites must pass the same quality standards as those for brand-name drugs.
Information about the availability of generic clopidogrel can be obtained from the manufacturers.
In this webinar, experts from Life Technologies will demonstrate several solutions using fluorescent probes to study key components of the apoptotic machinery.
Webinar Details
We will provide you with:
An overview of the features of apoptosis
Key parameters that can be measured to assay apoptosis
A comprehensive guide to available labeling and detection technologies for apoptosis research
Tips and tricks to best implement those technologies
Register for the webinar session that is convenient for you:
Session 1:
North America: May 24, 2012 at 10:00 am EDT (7:00 am PDT)
Europe: May 24, 2012 at 2:00 pm GMT
Bangalore: May 24, 2012 at 7:30 pm IST
Session 2:
North America: May 24, 2012 at 7:00 pm EDT(4:00 pm PDT)
Researchers have developed a way to pinpoint the molecules involved in forming a specific memory. The finding, in genetically engineered mice, gives scientists new insight into how memories are formed.
Newly synthesized proteins (green) traveled to mushroom-shaped spines in mouse hippocampus neurons. Researchers believe this process is key to strengthening a memory. Images after 1 (left), and 6 (right) hours of fear conditioning. Image courtesy of Drs. Mark Mayford and Naoki Matsuo, Scripps Research Institute.
For a memory to last long-term, the neural connections holding it need to be strengthened by incorporating new proteins. Some researchers have proposed that an experience creates a molecular “tag” at activated synapses, the connections between neurons. The tag allows synapses to capture newly made proteins and thus solidify a memory. But the molecular details of the process have been a mystery.
Previous studies suggested that proteins called AMPA-type glutamate receptors (AMPARs) strengthen memories by becoming part of the synapses that encode new memories. Drs. Mark Mayford and Naoki Matsuo of the Scripps Research Institute, supported in part by NIH's National Institute of Mental Health (NIMH), decided to explore the proteins further. They genetically engineered a strain of mice to make AMPARs that could be traced by their green glow.
The transgenic mice were taught to associate a specific environment with a foot shock, a process known as fear conditioning. This brief training produces a long-lasting memory that requires the brain’s hippocampus region. After fear conditioning had triggered new AMPARs deep in the neuron's nucleus, the researchers tracked where the newly made proteins went.
In the February 22, 2008, issue of the journal Science, the researchers reported that the newly synthesized AMPARs travel to and become captured by only certain hippocampus synapses—presumably the ones holding the new memory—within hours.
Synaptic connections are made onto small nubs on the neuron called spines. These spines come in 3 different shapes called thin, stubby and mushroom. The researchers found that the synapses receiving the new AMPARs were limited to the mushroom type.
The mushroom spines also figured prominently in the same neurons when fear conditioning was reversed by repeatedly exposing the animals to the feared situation without getting shocked—a procedure called extinction learning. This result shows that the same neurons activated when a fear is learned are also deactivated when it is lost.
The surge of receptors in mushroom spines appeared within hours of learning, suggesting that when mice learn something new, there are changes in some mushroom spines that allow them to capture newly synthesized AMPARs. The receptor surge was gone within 3 days, however, so other changes likely solidify the memory for the long term.
"Remarkably, this research demonstrates a way to untangle precisely which cells and connections are activated by a particular memory," said NIMH Director Dr. Thomas Insel. "We are actually learning the molecular basis of learning and memory."
*Corresponding author: Dr. Sandeep Mukherjee Section of Gastroenterology and Hepatology Nebraska Medical Center Omaha, NE 68198-3285, USA E-mail: smukherj@unmc.edu
Citation: Mukherjee S (2012) Protease Inhibitors for Recurrent Hepatitis C after Liver Transplantation-When Less is More. J Antivir Antiretrovir 4: i-i. doi:10.4172/ jaa.1000e101
The approval of boceprevir and telaprevir, two protease inhibitors for hepatitis C (HCV) treatment earlier this year, was met with virtually universal optimism as the addition of these medications will lead to a significantly improved chance of viral eradication in HCV genotype 1 patients [1]. However, this enthusiasm is yet to be embraced by the liver transplant community primarily due to the interaction between protease inhibitors and calcineurin inhibitors such as cyclosporine and tacrolimus. Boceprevir and telaprevir inhibit cytochrome P450 3A which metabolizes cyclosporine and tacrolimus leading to elevated and potentially lethal levels of these calcineurin inhibitors [2,3].
This was confirmed in an important phase I, open-label randomized, single sequence study earlier this year by Garg et al. [4] which merits further review. In part A of the study, ten healthy volunteers were administered a single 100mg oral dose of cyclosporine followed by an 8 day washout period before they were administered a single 10mg dose of cyclosporine and either a single dose of telapervir 750 mg or steadystate teleparevir 750mg every 8 hours. In part B, ten volunteers were administered a single dose of tacrolimus 0.5mg followed by a 14 day wash-out period before they were administerd a single 0.5mg dose of tacrolimus with telaprevir 750mg every 8 hours. Blood samples were obtained throughout the study for pharmacokinetic assessment and analysis. The investigators reported that co-administration of telaprevir with cyclosporine and tacrolimus, respectively, led to increased cyclosporine by 4.6 fold and tacrolimus by 70 fold, levels that are toxic and life-threatening.
This important study has confirmed the concerns of many transplant hepatologists. Despite the study’s findings, there were some important limitations, notably that it was conducted in healthy volunteers and not in liver transplant recipients with recurrent HCV. Extrapolating these results to a different patient population may be hard to justify. However, it seems more rather than less likely that HCV protease inhibitors should be prescribed with extreme caution in transplant patients-not only may drug metabolism be different from healthy volunteers but transplant recipients are also exposed to a variety of other medications that may interact with protease inhibitors independent of calcineurin inhibitors.
The concerns with HCV protease inhibitors were eloquently outlined by Michael Charlton, MD in an accompanying editorial this year [5]. Before we prescribe these medications, we need to inform patients and their families the following:
(a) Treatment is experimental as there are no studies in liver transplant patients
(b) Side effects may include organ failure and death from severe calcineurin toxicity
(c) Hepatic allograft rejection is a possibility as the dose and frequency for either calcineurin inhibitor has yet to be established
(d) Drug-Drug interactions between protease inhibitors and other medications used in transplant recipients are not fully recognized
(e) Only physicians well-versed with the management of liver transplant recipients and drug-drug interactions should care for these patients
(f) Treatment should only be reserved for patients with aggressive histological evidence of recurrent HCV in an attempt to prevent retransplantation [6].
Until the appropriate randomized trials are performed, transplant physicians should be extremely wary of prescribing these medications for patients with recurrent HCV. Human nature is such that it is inevitable that these medications will be used (or already have), in some cases probably appropriately as in patients where retransplantation or even re-retransplantation is to be avoided or contraindicated. Under these circumstances, adhering to the above check-list may lessen morbidity and mortality in this vulnerable group of patients.
CDC global health leadership brings the world's leading public health experts to a Guatemala cave, where rabid bats threaten human health. Elsewhere, CDC community workers keep a health watch over Kenya's poor; while in China, CDC scientists protect babies from a mysterious outbreak. These examples of CDC at work in the world help protect America and all from disease threats that respect no borders.
Physical activity is a proven way to relieve the pain and disability associated with arthritis, but many people do not have the confidence or knowledge about how to exercise safely. This video will help people with arthritis learn more about the benefits of physical activity and the types and amounts of exercise helpful for people with arthritis.
The U.S. Food and Drug Administration today approved Elelyso (taliglucerase alfa) for long-term enzyme replacement therapy to treat a form of Gaucher disease, a rare genetic disorder.
Gaucher disease occurs in people who do not produce enough of an enzyme called glucocerebrosidase. The enzyme deficiency causes fatty materials (lipids) to collect in the spleen, liver, kidneys, and other organs. The major signs of Gaucher disease include liver or spleen damage, low red blood cell counts (anemia), low blood platelet counts, and bone problems.
Elelyso is an injection that replaces the missing enzyme in patients with a confirmed diagnosis of Type 1 (non-neuropathic) Gaucher disease and should be administered by a health care professional every other week. Type 1 Gaucher disease is estimated to affect about 6,000 people in the United States.
“Today’s approval provides for a new enzyme replacement therapy for the select number of patients with Type 1 Gaucher disease,” said Julie Beitz, M.D., director of the Office of Drug Evaluation III in FDA’s Center for Drug Evaluation and Research. “It also demonstrates FDA’s commitment to developing treatments for rare diseases.”
Due to the small number of affected patients, the efficacy of Elelyso was evaluated in a total of 56 patients with Type 1 Gaucher disease enrolled in two clinical trials. Many of these patients continued treatment on a longer-term extension study.
In one multi-center, double-blind, parallel-dose trial, the efficacy of Elelyso for use as an initial therapy was evaluated in 31 adult patients who had not previously received enzyme replacement therapy. Patients were randomly selected to receive Elelyso at a dose of either 30 units per kilogram or 60 units/kg.
At both doses, Elelyso was effective in reducing spleen volume, the study’s primary endpoint, from baseline by an average of 29 percent in patients receiving the 30 units/kg dose and by an average of 40 percent in patients receiving the 60 units/kg dose after nine months of treatment. Improvements in liver volume, blood platelet counts, and red blood cell (hemoglobin) levels also were observed.
In the other study, the efficacy of Elelyso was assessed in 25 patients with Type 1 Gaucher disease who were switched from imiglucerase, another enzyme replacement therapy product. In this multi-center, open-label, single-arm trial, patients who had been receiving treatment with imiglucerase for at least two years were switched to Elelyso infusions every other week at the same dose of imiglucerase. Results showed Elelyso was effective in maintaining spleen and liver volumes, blood platelet counts, and hemoglobin levels over a nine month evaluation period.
The most common side effects reported during clinical studies were infusion reactions and allergic reactions. Symptoms of infusion reactions include headache, chest pain or discomfort, weakness, fatigue, hives, skin redness, increased blood pressure, back pain, joint pain, and flushing. As with other intravenous protein products, anaphylaxis has been observed in some patients during Elelyso infusions.
Other commonly observed side effects observed in greater than 10 percent of patients treated with Elelyso included upper respiratory tract infection, common cold-like symptoms (nasopharyngitis), joint pain (arthralgia), influenza, headache, extremity pain, back pain, and urinary tract infections.
Elelyso is manufactured and distributed by New York City-based Pfizer Inc., under license from Protalix BioTherapeutics Inc
The U.S. Food and Drug Administration today approved Levaquin (levofloxacin) to treat patients with plague, a rare and potentially deadly bacterial infection. The agency also approved the drug to reduce the risk of getting plague after exposure to Yersinia pestis, the bacterium that causes the disease.
Plague is extremely rare in most parts of the world, including the United States, with 1,000 to 2,000 cases worldwide each year. The three most common forms of plague are bubonic plague (infection of the lymph nodes), pneumonic plague (infection of the lungs), and septicemic plague (infection of the blood).
Primarily an animal disease, plague can be spread to humans through bites from infected fleas, contact with infected animals or humans, or laboratory exposure. Yersinia pestis also is considered a biological threat agent, which could potentially be used as a bioterrorism agent.
The FDA approved Levaquin for plague under the agency’s Animal Efficacy Rule, which allows efficacy findings from adequate and well-controlled animal studies to be used in cases where it is not feasible or ethical to conduct trials in humans. Because plague is such a rare disease, it would not be possible to conduct adequate efficacy trials in humans.
Levaquin’s approval was based on an efficacy study conducted in African green monkeys that were infected with the plague bacterium in a laboratory setting. Animals were randomly selected to receive a 10-day regimen of Levaquin or placebo within six hours of the onset of fever after being infected. The primary endpoint was survival at the end of the study. Of the 17 monkeys treated with Levaquin, 94 percent survived. None of the seven monkeys treated with placebo survived.
“Today’s approval broadens the available therapeutic treatments for plague,” said Edward Cox, M.D., M.P.H, director of the Office of Antimicrobial Products in FDA’s Center for Drug Evaluation and Research. “It also further demonstrates the usefulness of animal model studies to collect needed efficacy data in cases where human trials are not ethical or feasible.”
Levaquin’s safety has been evidenced by studies and post-marketing information for the drug’s existing medical uses. Common side effects reported in more than 3 percent of patients were nausea, headache, diarrhea, insomnia, constipation, and dizziness.
Serious but rare side effects include tendinitis and tendon rupture, worsening of muscle weakness in people with the neuromuscular disorder myasthenia gravis, allergic reactions, liver damage, abnormalities of the blood, effects on the nervous system, and abnormal heart rhythm. However, given that plague is a very serious and often deadly condition, the benefit of Levaquin for treating plague outweighs these potential risks.
The application for Levaquin was granted a priority review by the FDA. It joins streptomycin, doxycycline, tetracycline, and other antibacterial drugs in the tetracycline group as FDA-approved treatments for plague.
Levaquin is manufactured by Raritan, N.J.-based Janssen Pharmaceuticals Inc., a part of Johnson & Johnson.
A combination of 2 diabetes drugs, metformin and rosiglitazone, was more effective in treating youth with type 2 diabetes than metformin alone, according to a new study.
Rising childhood obesity in America has brought more cases of type 2 diabetes in youth. Type 2 diabetes heightens the risk for various health conditions, including coronary artery disease, stroke, nerve damage and kidney and eye disease. To fend off these complications, it's critical for young people with type 2 diabetes to control their blood glucose levels. However, because type 2 diabetes has been primarily an adult illness, information about how to effectively treat youth has been limited.
Several drugs are available to treat adults with type 2 diabetes. But only one oral medication—metformin—is approved by the U.S. Food and Drug Administration for treating young people with type 2 diabetes. The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study set out to test additional approaches to controlling blood glucose levels in youth. The study was funded primarily by NIH's National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
The researchers enrolled 699 youth, ages 10 to 17, who had type 2 diabetes for less than 2 years. All participants were considered overweight or obese. On average, their body mass index (BMI) was at the 98th percentile. The 85th percentile is considered overweight; 95th percentile is considered obese. The youth were randomly assigned to 3 treatment groups: metformin alone, metformin plus rosiglitazone (sold as Avandamet), and metformin plus intensive lifestyle changes aimed at weight loss and increased physical activity. Results appeared on April 29, 2012, in the early online edition of the New England Journal of Medicine.
The researchers were surprised to find that, over an average follow-up of 46 months, metformin alone maintained acceptable, long-term blood glucose control in only about half the youth. Also unexpected was the failure rate in the metformin plus lifestyle group, which was little better than metformin alone. In contrast, the failure rate was under 39% in the metformin and rosiglitazone group, a 25% reduction from metformin alone.
The use of rosiglitazone in adults has been restricted because studies linked its use in adults to a higher risk of heart attack and stroke. After a careful examination of the safety data, the TODAY Data and Safety Monitoring Board recommended that the study continue to test rosiglitazone. There were no cardiac events such as heart attack during the study.
“The results of this study tell us it might be good to start with a more aggressive drug treatment approach in youth with type 2 diabetes,” says TODAY study chair Dr. Philip Zeitler of Children's Hospital Colorado, Aurora. “We are learning that type 2 diabetes is a more aggressive disease in youth than in adults and progresses more rapidly, which could be why metformin alone had a higher than expected failure rate.”
Further study will be needed to see if more aggressive therapy will yield long-term benefits for youth with type 2 diabetes as they move into adulthood. Another question is why the rigorous lifestyle intervention didn’t bring the benefits that similar strategies have produced in adults. More research will be needed to design approaches that produce effective lifestyle changes for young people with type 2 diabetes.
Awake mental replay of past experiences is essential for making informed choices, suggests a study in rats. Without it, the animals’ memory-based decision-making faltered, say scientists funded by the National Institutes of Health. The researchers blocked learning from, and acting on, past experience by selectively suppressing replay — encoded as split-second bursts of neuronal activity in the memory hubs of rats performing a maze task.
"It appears to be these ripple-like bursts in electrical activity in the hippocampus that enable us to think about future possibilities based on past experiences and decide what to do," explained Loren Frank, Ph.D., of the University of California, San Francisco, a grantee of the NIH's National Institute of Mental Health (NIMH). "Similar patterns of hippocampus activity have been detected in humans during similar situations."
Frank, Shantanu Jadhav, Ph.D., and colleagues, report on their discovery online in the journal Science, Thursday, May 3, 2012.
"These results add to evidence that the brain encodes information not only in the amount of neuronal activity, but that its rhythm and synchronicity also play a crucial role," said Bettina Osborn, Ph.D., of the NIMH Division of Neuroscience and Basic Behavioral Science, which funded the research.
Frank and colleagues had discovered in previous studies that the rhythmic ripple-like activity in the hippocampus coincided with awake mental replay of past experiences, which occurs during lulls in the rats' activity. The same signal during sleep is known to help consolidate memories. So the researchers hypothesized that these awake ripple states are required for memory-guided decision-making. To test this in the current study, they selectively suppressed the ripple activity without disturbing other functions, while monitoring any effects on the animals’ performance in a maze task.
During breaks in trials when the rat was awake but inactive, areas in the brain's memory hub emitted split-second bursts of ripple-like electrical activity (SWRs). This indicated that the rat was mentally replaying an earlier experience in the maze. Individual neurons in the areas become associated with a particular place. These place cells spike when the animal is that place or — it turns out — is just mentally replaying the experience of being in that place. Embedded in the ripple-like signal above are place cells spiking in the same sequence as they did when the rat first walked through the maze (Color-coded hatch marks match the path in the maze.). Rats' performance in the maze task faltered when these awake mental replay events were blocked, revealing that they are important for memory-guided decision-making. Source: Shantanu Jadhav, Ph.D., University of California San Francisco
Individual neurons in certain areas of the hippocampus become associated with a particular place. These place cells fire when the animal is in that place or — it turns out — is just mentally replaying the experience of being in that place.
In the experimental situation, the rat needs to learn a rule to get a reward. It must remember which of two outer arms of a W-shaped maze it had visited previously and alternate between them – visiting the opposite arm after first visiting the center arm. The ripple activity occurs when rats are inactive during breaks between trials.
Place cells associated with the maze fire in rapid succession and in synchrony with other neurons in the neighborhood. The same place cells fire in the same sequence as they did when the rat first walked through the maze — suggesting that the rat is mentally replaying the earlier experience, but on a much faster timescale.
In the current study, an automatic feedback system shut down place cell firing, via mild electrical stimulation, whenever it detected ripple activity, thereby also preventing the replay of the maze memory. Without benefit of mental replay, rats' performance on the maze task deteriorated. The impairment was in the animals' spatial working memory — their ability to link immediate and earlier past experience to the reward. This ability was required to correctly decide which outside arm to visit after exiting the center arm during outbound trials.
The researchers propose that awake replay in the hippocampus provides such information about past locations and future options to the brain’s executive hub, the prefrontal cortex, which learns the alternation rule and applies it to guide behavior.
Even though the replay events in rats last just a fraction of a second, Frank notes that they are not unlike our own experience of memories, which tend to compress often lengthy events into snippets of just the highlights of what happened to us.
"We think the brain is using these same ripple-like bursts for many things," he explained. "It’s using them for retrieving memories, exploring possibilities — day-dreaming — and for strengthening memories."
The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit http://www.nimh.nih.gov.
The past few years have seen a boom in the number of papers published covering 3D cell culture, as researchers working in areas from cancer research to stem cells are increasingly seeing the benefits of this technique. This is due, in part, to the number of new tools designed to help researchers achieve better results. Bioscience Technology, along with 3D Biomatrix and AMSBIO, invite you to join us for a Webinar to discuss the latest advances.
Meghan Cuddihy, PhD, from 3D Biomatrix will discuss the use of matrix- free spheroid cultures, primarily in the context of cancer research and drug discovery. Specific detail will be given to 3D Biomatrix's Perfecta3D TM Hanging Drop Plates, which are versatile, matrix-free 3D well-plates designed to simplify and streamline spheroid formation, culture, and subsequent testing of the 3D cell cultures. The different applications and cell types for the Perfecta3D Hanging Drop Plates will be discussed, as will co-culture data and preliminary data on anti-cancer drug testing.
For applications where hanging drop are not applicable and to fulfill the increased demand for 3D cell cultures, AMSBIO supplies the most advanced and extensive range of 3D tools to the life science community. Erik Miljan, PhD, from Simply Cells Ltd assesses the impact on the physiological relevance of in vitro cell based models using traditional ECM proteins, recombinant Biomimetics hydrogels and other matrices like polystyrene scaffolds in drug discovery and disease modeling applications. Highlighting real examples including spheroid and neuronal stem cell culture, Dr. Miljan will demonstrate how the different 3D technologies that AMSBIO provides can help researchers to successfully perform the 3D applications they need.
REMINDER: Attend this live webcast and pose your critical questions to the panel of experts during the live Q&A session during the broadcast.
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February is American Heart Month—a time to reflect on the sobering fact that heart disease remains the number one killer of both women and men in the United States. The good news is you have the power to protect and improve your heart health.
NIH and other government agencies have been working to advance our understanding of heart disease so that people can live longer, healthier lives. Research has found that you can lower your risk for heart disease simply by adopting sensible health habits.
To protect your heart, the first step is to learn your own personal risk factors for heart disease. Risk factors are conditions or habits that make you more likely to develop a disease. Risk factors can also increase the chances that an existing disease will get worse.
Certain risk factors—like getting older or having a family history of heart disease—can’t be changed. But you do have control over some important risk factors such as high blood cholesterol, high blood pressure, smoking, excess weight, diabetes and physical inactivity. Many people have more than one risk factor. To safeguard your heart, it’s best to lower or eliminate as many as you can because they tend to “gang up” and worsen each other’s effects.
A large NIH-supported study published last month underscores the importance of managing your risk factors. Scientists found that middle-aged adults with one or more elevated risk factors, such as high blood pressure, were much more likely to have a heart attack or other major heart-related event during their remaining lifetime than people with optimal levels of risk factors.
“For example, women with at least 2 major risk factors were 3 times as likely to die from cardiovasculardisease as women with none or 1 risk factor,” says Dr. Susan B. Shurin, acting director of NIH’s National Heart, Lung and Blood Institute. “You can and should make a difference in your heart health by understanding and addressing your personal risk.”
To tackle your heart risk factors, it helps to know your numbers. Ask your health care provider to measure your blood cholesterol and blood pressure. Then determine if your weight is in the healthy range.
The higher your cholesterol level, the greater your risk for heart disease or heart attack. High blood cholesterol itself doesn’t cause symptoms, so you can’t know if your cholesterol is too high unless you have it tested. Routine blood tests can show your overall cholesterol level and separate levels of LDL (“bad”) cholesterol, HDL (“good”) cholesterol and triglycerides. All of these blood measurements are linked to your heart health.
High blood pressure (hypertension) is another major risk factor for heart disease, as well as for stroke. High blood pressure is often called the “silent killer” because, like high cholesterol, it usually has no symptoms. Blood pressure is always reported as 2 numbers, and any numbers above 120/80 mmHg raise your risk of heart disease and stroke.
“Scientific evidence is strong that controlling high blood cholesterol and high blood pressure prevents cardiac events such as heart attacks,” says Dr. Michael Lauer, a heart disease specialist at NIH.
Your weight is another important number to know. To find out if you need to lose weight to reduce your risk of heart disease, you’ll need to calculate your body mass index (BMI, a ratio of weight to height). This NIH web page can help: www.nhlbisupport.com/bmi/bmicalc.htm. A BMI between 25 and 29.9 means that you’re overweight, while a BMI of 30 or higher means obesity.
Next, take out a tape measure. A waist measurement of more than 35 inches for women and 40 inches for men raises the risk of heart disease and other serious health conditions. Fortunately, even a small weight loss (between 5% and 10% of your current weight) can help lower your risk.
NIH has many tools available to help you aim for a healthy weight, including physical activity tips and a menu planner. To learn more, visit http://healthyweight.nhlbi.nih.gov/.
A heart-healthy diet includes a variety of fruits, vegetables and whole grains, as well as lean meats, poultry, fish, beans and fat-free or low-fat dairy products. Try to avoid saturated fat, trans fat, cholesterol, sodium (salt) and added sugar.
Regular physical activity is another powerful way to reduce your risk of heart-related problems and enjoy a host of other health benefits. To make physical activity a pleasure rather than a chore, choose activities you enjoy. Take a brisk walk, play ball, lift light weights, dance or garden. Even taking the stairs instead of an elevator can make a difference.
“At least 2 and a half hours a week of moderate-intensity physical activity can lower your risk of heart disease, stroke, hypertension and diabetes—a winner on multiple counts,” says Dr. Diane Bild, a cardiovascular epidemiologist at NIH.
If you have diabetes, it’s important to keep your blood sugar, or glucose, under control. About two-thirds of people with diabetes die of heart or blood vessel disease. If you’re at risk for diabetes, modest changes in diet and level of physical activity can often prevent or delay its development.
If you happen to be a smoker, the best thing you can do for your heart is stop. People who smoke are up to 6 times more likely to suffer a heart attack than nonsmokers. The risk of heart attack increases with the number of cigarettes smoked each day.
The good news is that quitting smoking will immediately begin to reduce your risk, and the benefit in reduced risk will continue to increase over time. Just one year after you stop smoking, your risk will have dropped by more than half.
Beyond controlling your risk factors, you should be alert to certain symptoms and get checked by a doctor. Common signals that something‘s wrong with your heart include angina—pain in the chest, shoulders, arms, neck, jaw or back—as well as shortness of breath, irregular heartbeat or palpitations (arrhythmia) and fatigue.
Be aware that the symptoms of a heart attack can vary from person to person. If you’ve already had a heart attack, your symptoms may not be the same if you have another one.
Finally, don’t forget that you can influence your loved ones’ heart health by setting an example. Do you have children, grandchildren or other young people who look up to you? If you follow a heart-healthy lifestyle, it’s more likely that they will, too. Because heart disease begins in childhood, one of the best things you can do for those you love is to help children build strong bodies and healthy habits.
The bottom line is, it’s never too late to take steps to protect your heart. It’s also never too early. Start today to keep your heart strong. Talk to your doctor about your risk and to create an action plan. Love your heart.
CDC Continues to work with its partners in the Global Polio Eradication Initiative (GPEI) including Rotary International, WHO, UNICEF, and the Bill and Melinda Gates Foundation, to rid the world of polio forever. In surpassing a year without detecting a single case of wild poliovirus, India has achieved a major milestone. This clearly demonstrates that strong political will, concerted and sustained high quality effort, and continued commitment can stop polio.
Suicide is tragic. It cuts a life short, and it devastates the family, friends and loved ones left behind. Those who survive a suicide attempt might end up with severe disability or other injuries. The children of people who die by suicide are more likely to later die by suicide themselves. With such extreme consequences, why would anyone make the dire decision to choose death over life?
That’s a question scientists have been struggling to answer for decades. “When you’re in a suicidal state, you’re kind of closing down your options. You see it as the only solution. You’re not really able to entertain other ideas,” says Dr. Jane Pearson, who heads a suicide research consortium at NIH. “What’s the science behind that? What’s happening in the brain that leads people to think so dysfunctionally?”
Only 20 years ago, little was known about the biology of suicide. But NIH-funded research has helped to open up new avenues for exploring the underlying causes of suicide. While the biological details are still being worked out, scientists have uncovered many clues to identify people at greatest risk for suicidal thoughts and actions.
Recognizing those at risk is essential. Suicide is the 10th leading cause of death nationwide, and it’s the 3rd leading cause of death among adolescents. Nearly 37,000 Americans died by suicide in 2009, according to the U.S. Centers for Disease Control and Prevention. More than half of those deaths were from firearms.
People of all genders, ages and ethnicities are at risk for suicide. Women are more likely than men to attempt suicide, but men are more likely to die by suicide. That’s because men often choose deadlier methods, such as firearms or suffocation.
“The highest risk groups are older men,” says Pearson. “In fact, white men who are 85 and older have a rate of suicide that’s 4 times the national average.”
Suicide risk is also higher among people who have certain mental disorders, including schizophrenia and bipolar disorder. Depression affects more than half of those who die by suicide. Other risk factors include a prior suicide attempt, a family history of suicide, substance abuse, or having guns or other firearms in the home.
In the past, many scientists believed that suicide was a terrible side effect of other mental disorders. But why is it that only a small proportion of people with depression or other mental conditions attempt suicide? A growing body of evidence suggests that there is something unique about their biology that can tip them over the edge.
“We’ve found many systems in the brain that are broken with suicide, especially in the front part above the eye—called the orbital prefrontal cortex. That area of the brain is involved in inhibiting behaviors that are damaging, like being unable to inhibit the urge to kill oneself,” says Dr. Victoria Arango, a suicide researcher at the New York State Psychiatric Institute.
Over the decades, Arango and her colleagues have conducted detailed studies of brain structure and biology in hundreds of suicide victims. They’ve found that certain brain regions in suicide have fewer nerve cells and altered receptors for neurotransmitters. Abnormalities related to the neurotransmitter serotonin have been linked to suicide in many studies. Scientists have not yet figured out if these flaws in serotonin directly contribute to suicide or—more likely—if serotonin is one part of a complicated chemical pathway to suicide. Serotonin is also believed to play a key role in depression and response to stress and trauma.
“Stress and trauma certainly play a big role in suicide, especially early life stress,” says Dr. Douglas Meinecke, an NIH scientist who studies the molecular details of mental disorders. Several research teams have found evidence that traumatic childhood experiences—such as abuse or violence—can “tag” certain genes in the brain. These tags, called epigenetic markers, are actually molecules that attach to genes. They can have a lasting effect on whether the genes are turned off or on.
Some NIH-funded studies have shown that suicide victims who were abused as children have unique epigenetic markers on certain genes. These markers were not found in suicide victims with no history of childhood abuse or in people who died in accidents. More research into how stress affects genes and suicide risk might offer new chances for early intervention.
Current approaches to treating or preventing suicide generally aim to relieve the accompanying mental condition or other risk factors. “If you focus on making people who have mental disorders as well as they can be, managing life as well as they can or reducing their suicidal thoughts, you can greatly reduce suicide overall,” says Meinecke.
Medications—such as antidepressants and antipsychotics—can help. Psychotherapy, or “talk therapy,” can also be effective. One type, called cognitive behavioral therapy, can help people learn new ways to deal with stressful situations by training them to consider alternative actions when thoughts of suicide arise.
One of the most effective tools for preventing suicide is to know the warning signs and take quick action to get the person into treatment. “One of the biggest indicators of suicide risk is when somebody begins talking about suicide,” says Dr. David Brent, a psychiatrist at the University of Pittsburgh who studies suicide in families. “We used to think that talking about suicide meant you weren’t going to do it, but it’s really the opposite. Other warning signs include withdrawal from usual activities, a change in mood or a change in sleep patterns.”
Never ignore someone’s talk of suicide. You can ask directly if the person has ever thought of harming himself or herself. Most people will answer honestly, and the question itself won’t push a person to attempt suicide.
See the “Wise Choices” box to learn more, or call the National Suicide Prevention Lifeline at 1-800-273-TALK (8255). This free, federally funded service is available to anyone, 24 hours a day, 7 days a week. All calls are confidential.
This FDA Consumer Update video provides helpful tips to avoid the three main types of interactions: drugs with food and beverages, drugs with dietary supplements, and drugs with other drugs. Learn more at http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm096386.htm
The U.S. Food and Drug Administration today approved generic versions of the blood thinning drug Plavix (clopidogrel bisulfate), which helps reduce the risk of heart attack and stroke by making it less likely that platelets in the blood will clump and form clots in the arteries. 
The U.S. Food and Drug Administration today approved Elelyso (taliglucerase alfa) for long-term enzyme replacement therapy to treat a form of Gaucher disease, a rare genetic disorder. 
