FDA Rare Disease Patient Advocacy Day

On March 01, 2012, the Food and Drug Administration (FDA) will celebrate the fifth annual Rare Disease Day by hosting a "FDA Rare Disease Patient Advocacy Day" to engage and educate the rare disease community on regulatory processes related to rare diseases.

This meeting is intended to enhance the awareness of the rare disease community as to FDA’s roles and responsibilities in the development of products (drugs, biological products and devices) for the diagnosis, prevention, and/or treatment of rare diseases or conditions.

This educational meeting will consist of live and interactive simultaneous webcast of presentations provided by FDA experts from various Centers and Offices, as well as from outside experts. The interactive meeting will include two general panel discussion sessions, as well as afternoon breakout sessions for more in-depth information on the roles of FDA. In addition, on-site attendees will have an opportunity during lunch to engage with FDA and outside experts in a small group setting.

• For more information about Rare Disease Day, see Rare Diseases Take Spotlight in Annual Event.
• For more information about the History of FDA and Milestones In U.S. Food and Drug Law, see About the FDA

Registration:

While attendance is free, registration is required to attend the event.

Register for FDA Rare Disease Patient Advocacy Day

If you need sign language interpretation during this meeting, please contact Megan McNamee at mmcnamee@icfi.com by February 15, 2012.

Source: U.S. FDA

Prescription drugs can be Dangerous

Using Autoinjectors to Treat Seizures

Drug delivery into muscle using an autoinjector—akin to the EpiPen used to treat serious allergic reactions—can be a fast, effective way to stop prolonged epileptic seizures. The finding provides a safe tool to treat people quickly during an emergency.

Epilepsy is a brain disorder in which nerve cells in the brain sometimes signal abnormally. When the normal pattern of neuronal activity becomes disturbed, it can lead to convulsions and muscle spasms. Status epilepticus is a prolonged seizure lasting longer than 5 minutes. This potentially life-threatening emergency causes 55,000 deaths each year.

Anticonvulsant drugs are typically delivered intravenously (IV) as a first-line treatment for status epilepticus. But starting an IV in a patient having a seizure can be challenging and waste precious time. Giving an intramuscular shot is easier, faster and more reliable.

A team of researchers led by Dr. Robert Silbergleit of the University of Michigan in Ann Arbor sought to determine whether an intramuscular injection, which quickly delivers anticonvulsant medicine into a patient's thigh muscle, is as safe and effective as giving medicine directly into a vein. The Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART) compared how well delivery by each method stopped patients' seizures by the time the ambulance arrived at the emergency department. The research was funded primarily by NIH’s National Institute of Neurological Disorders and Stroke (NINDS).

The study compared 2 medications proven effective at controlling seizures, both from the benzodiazapine class of sedating anticonvulsant drugs. Lorazepam, which must be given by IV, is the current standard of care. Midazolam, which is rapidly absorbed from muscle, was delivered by injection. The trial involved more than 79 hospitals, 33 emergency medical services agencies, more than 4,000 paramedics and almost 900 patients ranging in age from several months to 103 years old.

In the February 16, 2012, issue of the New England Journal of Medicine, the researchers reported that 73% of patients in the group receiving midazolam were seizure-free upon arrival at the hospital, compared to 63% who received IV treatment with lorazepam. Patients treated with midazolam were also less likely to require hospitalization than those receiving IV lorazepam. Among those admitted, both groups had similarly low rates of recurrent seizures.

“Few other areas of medicine are as time-dependent as injury to the brain,” Silbergleit says. “In epilepsy, even a few minutes can be important. With every minute the seizure continues, it becomes harder to stop. RAMPART offers first responders an important treatment tool that will have a meaningful impact on the lives of many people with epilepsy.”

These results also have implications for public health preparedness. The trial shows that autoinjectors can provide a practical way to treat hundreds of people quickly during a widespread emergency, such as a chemical or biological attack.

Source: NIH

Scientists Find Target for Resveratrol

 

Resveratrol, a compound found most famously in grapes and red wine, seems to ward off several age-related diseases. However, its mechanism of action has been elusive. Researchers have now found a direct molecular target for the compound. The finding may lead to drugs that can prevent certain age-related health problems.

People can develop a variety of metabolic diseases as they age, including type 2 diabetes and heart disease. In animal studies, severely restricting calories can help prevent these diseases. Over the last decade, scientists have found that resveratrol mimics calorie restriction in some ways. It seems to affect the activity of proteins called sirtuins. Sirtuins control several biological pathways and are known to be involved in the aging process.

Recent studies uncovered intermediate steps between resveratrol and sirtuins. A key step in this pathway is an enzyme called AMPK, which regulates energy levels in the cell. However, the link between resveratrol and AMPK has been a mystery. To investigate, a research team led by Dr. Jay H. Chung of NIH's National Heart, Lung and Blood Institute (NHLBI) set out to find resveratrol's target. Their study appeared in the February 3, 2012, issue ofCell.

The researchers methodically traced metabolic activity in cells treated with resveratrol. They were able to identify an enzyme called PDE4 in the skeletal muscle as the principal target for the health benefits of resveratrol. Resveratrol inhibits PDE4, which raises levels of an important cell signaling molecule called cAMP. Levels of cAMP normally rise when cells get the signal that blood glucose levels are low. Resveratrol thus activates one of the same biochemical pathways as a low-calorie diet. This pathway ultimately activates AMPK and sirtuins.

To confirm their findings, the scientists gave mice rolipram, a drug known to inhibit PDE4. Like resveratrol, the drug protected mice from the ill effects of a high-fat diet. Mice on a high-fat diet normally become obese and develop glucose intolerance, a hallmark of type 2 diabetes. Mice given the drug stayed healthy.

As this study shows, the biochemical pathways affected by resveratrol are complex and far-reaching. As a natural product, resveratrol likely has additional targets, which could lead to side effects. These findings may now help researchers design effective drugs without those potential problems.

“Resveratrol has potential as a therapy for diverse diseases such as type 2 diabetes, Alzheimer’s disease and heart disease,” says Chung. “However, before researchers can transform resveratrol into a safe and effective medicine, they need to know exactly what it targets in cells.”

A PDE4 inhibitor that is 30,000 times more potent than resveratrol has recently been approved by the FDA for treating chronic obstructive pulmonary disease. Chung's group is now planning a clinical trial to test the inhibitor in obese people at risk for developing type 2 diabetes.

Source: U.S. FDA

The Dangers of Unpasteurized Milk

Milk and milk products provide a wealth of nutrition benefits. But unpasteurized milk can harbor dangerous microorganisms that can pose serious health risks to you and your family

Source: U.S. FDA

How FDA's Science and Engineering Labs Solve Public Health Problems: The Huber Needle Story

Source: U.S. FDA

Grapefruit Juice and Medicine May Not Mix

 

Grapefruit juice can be part of a healthful diet—most of the time. It has vitamin C and potassium—substances your body needs to work properly. But it isn’t good for you when it affects the way your medicines work.          

 

Grapefruit juice and fresh grapefruit can interfere with the action of some prescription drugs, as well as a few non-prescription drugs.

This interaction can be dangerous, says Shiew Mei Huang, acting director of the Food and Drug Administration’s Office of Clinical Pharmacology. With most drugs that interact with grapefruit juice, “the juice increases the absorption of the drug into the bloodstream,” she says. “When there is a higher concentration of a drug, you tend to have more adverse events.”

For example, if you drink a lot of grapefruit juice while taking certain statin drugs to lower cholesterol, too much of the drug may stay in your body, increasing your risk for liver damage and muscle breakdown that can lead to kidney failure.

Drinking grapefruit juice several hours before or several hours after you take your medicine may still be dangerous, says Huang, so it’s best to avoid or limit consuming grapefruit juice or fresh grapefruit when taking certain drugs.

Examples of some types of drugs that grapefruit juice can interact with are:

• some statin drugs to lower cholesterol, such as Zocor (simvastatin), Lipitor (atorvastatin) and Pravachol (pravastatin)
• some blood pressure-lowering drugs, such as Nifediac and Afeditab (both nifedipine)
• some organ transplant rejection drugs, such as Sandimmune and Neoral (both cyclosporine)
• some anti-anxiety drugs, such as BuSpar (buspirone)
• some anti-arrhythmia drugs, such as Cordarone and Nexterone (both amiodarone)
• some antihistamines, such as Allegra (fexofenadine)

Grapefruit juice does not affect all the drugs in the categories above. Ask your pharmacist or other health care professional to find out if your specific drug is affected.

 

Too High or Too Low Drug Levels

Many drugs are broken down (metabolized) with the help of a vital enzyme called CYP3A4 in the small intestine. Certain substances in grapefruit juice block the action of CYP3A4, so instead of being metabolized, more of the drug enters the bloodstream and stays in the body longer. The result: potentially dangerous levels of the drug in your body.

The amount of the CYP3A4 enzyme in the intestine varies from one person to another, says Huang. Some people have a lot, and others have just a little—so grapefruit juice may affect people differently when they take the same drug.
While scientists have known for several decades that grapefruit juice can cause a potentially toxic level of certain drugs in the body, Huang says more recent studies have found that the juice has the opposite effect on a few other drugs.

“Grapefruit juice reduces the absorption of fexofenadine,” says Huang, decreasing the effectiveness of the drug. Fexofenadine (brand name Allegra) is available in both prescription and non-prescription forms to relieve symptoms of seasonal allergies. Fexofenadine may also be less effective if taken with orange or apple juice, so the drug label states “do not take with fruit juices.”

Why this opposite effect?
It involves the transportation of drugs within the body rather than their metabolism, explains Huang. Proteins in the body known as drug transporters help move a drug into cells for absorption.

Substances in grapefruit juice block the action of a specific group of transporters. As a result, less of the drug is absorbed and it may be ineffective, Huang says.

When a drug sponsor applies to FDA for approval of a drug, the sponsor submits data on how its drug is absorbed, metabolized and transported says Huang. “Then we can decide how to label the drug.”

FDA has required some prescription drugs to carry labels that warn against consuming grapefruit juice or fresh grapefruit while using the drug, says Huang. And the agency’s current research into drug and grapefruit juice interaction may result in label changes for other drugs as well.

Tips for Consumers

• Ask your pharmacist or other health care professional if you can have fresh grapefruit or grapefruit juice while using your medication. If you can’t, you may want to ask if you can have other juices with the medicine.
• Read the Medication Guide or patient information sheet that comes with your prescription medicine to find out if it could interact with grapefruit juice. Some may advise not to take the drug with grapefruit juice. If it’s OK to have grapefruit juice, there will be no mention of it in the guide or information sheet.
• Read the Drug Facts label on your non-prescription medicine, which will let you know if you shouldn’t have grapefruit or other fruit juices with it.
• If you must avoid grapefruit juice with your medicine, check the label of bottles of fruit juice or drinks flavored with fruit juice to make sure they don’t contain grapefruit juice.
• Seville oranges (often used to make orange marmalade) and tangelos (a cross between tangerines and grapefruit) affect the same enzyme as grapefruit juice, so avoid these fruits as well if your medicine interacts with grapefruit juice.

Source: U.S. FDA

Teaching Kids About Using Medicine Safely

Source: U.S. FDA

Jaundice and Your Newborn: What every parent should know

New parents talk about Jaundice and discuss important information that every parent should know

Source: CDC

Fragile X Syndrome

This video contains information about the causes of Fragile X Syndrome.

Seven Deadly Myths…

Seven Deadly Myths, produced in 2000 and hosted by former model, entrepreneur and smoking cessation advocate Christy Turlington, is a 17-minute closed-captioned video that explores some of the common myths about smoking and empowers women to become or stay smoke-free.

Source: CDC

The Republic Day celebrations

An impressive display of armour and unmanned aerial vehicles recently added to India’s military prowess was on full display at the 63rd Republic Day parade today
Business Line : Industry & Economy / Economy : The Republic Day celebrations

Looking Inside Viruses

Since the discovery of the microscope, scientists have tried to visualize smaller and smaller structures to provide insights into the inner workings of human cells, bacteria and viruses. Now, researchers have developed a new way to see tiny structures within viruses.

Image: Computer reconstruction of a virus shell (gray) and inner structure (magenta). In the background, a cryo-electron micrograph of viral particles with inner structures bubbling from radiation damage.

Conventional cryo-electron microscopy (cryo-EM) has allowed researchers to image the surface of viruses in great detail. But scientists hadn't been able to clearly visualize structures inside viruses. Cryo-EM procedures use radiation, and higher doses damage viruses, destroying the very structures researchers would like to view.

A team led by Dr. Alasdair Steven of NIH's National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and Dr. Lindsay Black at the University of Maryland Medical School was studying a type of virus that infects bacteria and so might one day be used to combat pathogens. Past studies showed that the virus, called ϕKZ, contains a cylindrical protein structure called the inner body. Those studies, however, used disrupted viruses. The inner body can't be distinguished from the DNA that surrounds it in intact viruses using conventional cryo-EM.

In the January 13, 2012, issue of Science, the researchers described how they were able to turn the problem of radiation damage into an asset. They realized that the proteins inside the virus are more sensitive than DNA to radiation damage. After recording images of the virus with low doses of radiation, they used higher doses. As the inner structure deteriorated, it appeared as a cylinder of bubbles. The team was able to superimpose the images and, using 3-D computer reconstruction, clearly visualize the viral structure. The investigators call their technique bubblegram imaging.

Based on the shape and position of the inner body, the researchers believe that it helps organize DNA into its compact structure. In the future, bubblegram imaging may yield further insights into the inner workings of viruses and suggest strategies for developing novel therapies.

The scientists anticipate other uses for bubblegram imaging as well. For example, it could be used to visualize the interactions of proteins with DNA in human cells.

“This new cryo-EM procedure renders previously invisible proteins visible and, thus, will provide new understanding of cell biology,” Steven says.

Source: NIH

FDA approves Kalydeco to treat rare form of cystic fibrosis

Breakthrough therapy targets defective protein

The U.S. Food and Drug Administration today approved Kalydeco (ivacaftor) for the treatment of a rare form of cystic fibrosis (CF) in patients ages 6 years and older who have the specific G551D mutation in the Cystic Fibrosis Transmembrane Regulator (CFTR) gene.

CF is a serious genetic disorder affecting the lungs and other organs that ultimately leads to an early death. It is caused by mutations (defects) in a gene that encodes for a protein called CFTR that regulates ion (such as chloride) and water transport in the body. The defect in chloride and water transport results in the formation of thick mucus that builds up in the lungs, digestive tract and other parts of the body leading to severe respiratory and digestive problems, as well as other complications such as infections and diabetes.

CF, which affects about 30,000 people in the United States, is the most common fatal genetic disease in the Caucasian population. About 4 percent of those with CF, or roughly 1,200 people, are believed to have the G551D mutation.

“Kalydeco is an excellent example of the promise of personalized medicine – targeted drugs that treat patients with a specific genetic makeup,” said FDA Commissioner Margaret A. Hamburg, M.D. “The unique and mutually beneficial partnership that led to the approval of Kalydeco serves as a great model for what companies and patient groups can achieve if they collaborate on drug development.”

The FDA reviewed and approved Kalydeco in approximately three months under the agency’s priority review program that is designed to expedite the review of drugs. The priority review program uses a six-month review, instead of the standard 10 months, for drugs that may offer significant advances in treatment over available therapy.

Kalydeco was approved ahead of the drug’s April 18, 2012 prescription user fee goal date and is designated as an orphan drug, which identifies the disease as affecting fewer than 200,000 people in the United States.

In patients with the G551D mutation, Kalydeco, a pill taken two times a day with fat-containing food, helps the protein made by the CFTR gene function better and as a result, improves lung function and other aspects of CF such as increasing weight gain.

“Kalydeco is the first available treatment that targets the defective CFTR protein, which is the underlying cause of cystic fibrosis,” said Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research. “This is a breakthrough therapy for the cystic fibrosis community because current therapies only treat the symptoms of this genetic disease.”

Two 48-week, placebo-controlled clinical studies involving 213 patients, one in patients ages 12 years and older and another in patients ages 6 years to 11 years, were used to evaluate the safety and efficacy of Kalydeco in CF patients with the G551D mutation. In both studies, treatment with Kalydeco resulted in significant and sustained improvement in lung function.

Kalydeco is effective only in patients with CF who have the G551D mutation. It is not effective in CF patients with two copies of the F508 mutation in the CFTR gene, which is the most common mutation that results in CF. If a patient’s mutation status is not known, an FDA-cleared CF mutation test should be used to determine whether the G551D mutation is present.

The most common side effects of Kalydeco include upper respiratory tract infection, headache, stomach ache, rash, diarrhea, and dizziness.

Kalydeco is manufactured by Vertex Pharmaceuticals Inc. of Cambridge, Mass.

Source: U.S. FDA