February 25, 2011
NIH Podcast Episode #0128
Balintfy: Welcome to episode 128 of NIH Research Radio with news about the ongoing medical research at the National Institutes of Health – the nation's medical research agency. I'm your host Joe Balintfy. And coming up in this episode, a personalized medication that’s effective for treating alcoholism, the incidence of postpartum depression, the importance of heart health for women, and an important perspective on Alzheimer’s disease research. But first, this news update. Here’s Craig Fritz.
Fritz: A study funded by the National Institute of Allergy and Infectious Diseases has found that spraying malaria-transmitting mosquitoes with a genetically modified fungus can kill the malaria parasite without harming the mosquito. Malaria causing parasites were found in just 25 percent of mosquitoes that were sprayed with the modified fungus compared to 94 percent of untreated mosquitoes. Additionally, the spray reduced the density of parasites in the mosquitoes by 95 percent compared to an unmodified fungal spray. Researchers say that the main goal now is to get the new technology into the field. They will run additional tests to make sure they are using the most potent malaria fighting combination. Malaria kills over 780,000 people each year and is found in 106 countries around the globe. A majority of the 225 million annual cases occur in sub-Saharan Africa.
Researchers funded by the National Hearth Lung and Blood Institute have found that abnormal heart rate turbulence is associated with an increased risk of heart disease death in otherwise low-risk, older individuals. Heart rate turbulence reflects how well the heart reacts to occasional premature contractions. Nearly 1300 study participants considered at low risk of heart disease based on traditional risk factors were on average 8 to 9 times more likely to die of heart disease during the 14-year follow-up period if they had abnormal heart rate turbulence. traditional risk factors include age, gender, high blood cholesterol, high blood pressure, obesity, diabetes, and smoking. At the beginning of the study, participants underwent 24-hour monitoring of their hearts’ electrical activity through a small monitor attached to their skin. By analyzing the heart's electrical signals, physicians measured the magnitude of the initial heart rate jump and the speed at which heart rate returned to normal to determine if the heart rate turbulence response was abnormal. Researchers don't yet know if abnormal heart rate turbulence can be treated or prevented and currently, this type of measurement is not widely available. More research is needed to determine if this finding can be replicated in other populations.
For this NIH news update—I’m Craig Fritz
Balintfy: News updates are compiled from information at www.nih.gov/news. Coming up, we’ll learn how Alzheimer’s disease research has advanced over the past decade, and have a couple reports important to women – about postpartum depression, and heart disease risk. Up next, how genetics can predict the success of a potential alcoholism treatment.
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Gene variants predict treatment success for alcoholism medication
Balintfy: In a recent study, researchers showed that alcohol dependent individuals who possess specific gene variants have a much better response to an experimental medication. Researchers say the findings demonstrate the promise of personalized medicine. Wally Akinso has the details.
Akinso: The effectiveness of an experimental treatment for alcoholism depends on the genetic make up of people who receive it.
Litten: This was a state of the art design, studying the effects of a drug called ondansetron.
Akinso: Dr. Raye Litten is a health scientist administrator at the National Institute on Alcohol Abuse and Alcoholism.
Litten: To be able to indentify patients who respond say to a medication and perhaps even identify those who may have an adverse reaction will enable clinicians to administer the drug in a more efficient, effective and safer manner.
Akinso: Ondansetron is currently used to treat nausea and vomiting, often following chemotherapy. It works by blocking receptors for the brain chemical, serotonin. This NIAAA study extends the researchers' previous work on the role the brain's serotonin system plays in alcohol misuse. Changes in the serotonin levels in the brain can alter moods, including the rewarding effects of alcohol. Specifically serotonin transporter variants designated as LL, S and TT have been associated with more severe drinking problems.
Litten: These are a site that occurs in the serotonin transporter gene; actually a functional polymorphic region where you actually can get functional changes.
Akinso: Researchers performed genetic analyses to determine which serotonin transporter gene variants, a protein that regulates the concentration of the serotonin between nerve cells, were carried by each subject, then randomly assigned each subject to treatment regimens with ondansetron or placebo.
Litten: Those who had the LL genotype says versus those who had the short version had fewer drinks per drinking day and more days abstinent in the presence of ondansetron than those who even took ondansetron and had the short version or the S version.
Akinso: Researchers have shown that variations in the gene that encodes the serotonin transporter can significantly influence drinking intensity according to Dr. Litten.
Litten: They also did better than those who took the placebo. Interestingly when you add the second site to that those who had the TT version along with the LL version even had a better outcome. It was like it was an interaction. In fact it appears that the effects by having both the LL and TT you can almost double your effect size with that combination.
Akinso: Dr. Litten says by being able to do genetic screening beforehand clinicians can eliminate a great deal of trial and error approach to prescribing medicine. He adds that this kind of personalized medicine allows clinicians to better predict a successful treatment option. For more information, visit www.niaaa.nih.gov. This is Wally Akinso at the National Institutes of Health, Bethesda, Maryland.
Balintfy: Now a couple reports important for women: First, postpartum depression may be one of the most under-recognized and under-treated disorders. Yet, it impacts the lives of hundreds of thousands of new mothers. The biological changes in mothers after childbirth are very significant and important. But for some parents, this postpartum period can lead to a type of depression thought to be associated with drastic changes in hormone levels. Dr. Peter Schmidt at the National Institute of Mental Health says postpartum depression is estimated to affect roughly 13-percent of all new mothers.
Schmidt: So each year in the United States there are approximately half a million women who are at risk of developing postpartum depression. So, clearly this is an important condition to the public health of this country, these are prevalent conditions that are associated with considerable morbidity.
O’Leary: Many women, probably at least fifty percent, experience what are called the baby blues for a week or two after giving birth.
Balintfy: Kathleen O’Leary is with the Women’s Mental Health Program at NIMH. She explains that women may feel tearful, emotionally very sensitive, overwhelmed or just not like themselves.
O’Leary: And this is not unusual. If these symptoms go on for more than two weeks or become more intense or women start experiencing some of the other symptoms of depression, then they should really seek help.
Balintfy: Symptoms of depression can vary depending on the individual but can include sad, anxious or “empty” feelings, feelings of hopelessness, pessimism, or worthlessness. O’Leary adds that what starts out as sleep deprivation issues for new mothers, can transform into the more serious problems of depression.
O’Leary: If someone feels that they would be better off dead or that others would be better off without them, then that is the most serious sign that means that a medical professional needs to be consulted about this as soon as possible.
Balintfy: Research has shown some women are at greater risk of experiencing postpartum depression. That includs women who have had postpartum depression with a previous child; women who have had depression, whether treated or untreated, at another time in their lives; as well as women who have bipolar disorder. NIMH investigators have conducted extensive research into postpartum depression, its causes and possible treatments. Dr. Schmidt explains that current research includes the indication that estradiol, a form of estrogen, has a rapid antidepressant effect on women with postpartum depression.
Schmidt: Because of our earlier work it suggested that declining levels of estrogen during the postpartum around delivery might contribute to triggering the onset of depression. And there had been some preliminary open trials showing that estradiol may have an effective antidepressant action in some of these women. So, we have a study now in which we’re using estradiol, physiological levels, so comparable to what a woman would be exposed to during her normal cycle and we give that in a controlled trial to women who have current postpartum depression.
Balintfy: The possibility of successful hormone treatment along with effective therapy has been very encouraging for many women. For more information on postpartum depression and NIMH research on depression, visit www.nimh.nih.gov.
NIH encourages women to take charge of their heart health
Balintfy: Also important to women, heart health. The National Heart Lung and Blood Institute is celebrating one of its most prestigious campaigns. Cherry Graziosi has this report.
Graziosi: The National Heart Lung and Blood Institute’s Heart Truth campaign is marking its seventh year and the message is being heard loud and clear.
Cook: The Heart Truth campaign is an awareness campaign that was really a landmark opportunity that NHLBI began to make awareness of women’s heart disease really a reality for all women throughout the country.
Graziosi: Dr. Nakela Cook, a cardiologist at NHLBI, says since the campaign began in 2002 the rate of awareness has doubled among women recognizing heart disease as their number one killer.
Cook: We also know that when people are aware they’re more likely to take action to reduce their risks by doing things such as changing their lifestyle and changing their diet, increasing their exercise – taking steps to understand what the risk factors are and having personal conversations with their doctors. All of this has increased as a result of this.
Graziosi: Dr. Cook says the risk factors haven’t changed from years past.
Cook: The traditional risk factors include high blood cholesterol or triglyceride levels, having a family history of heart disease, women being over the age of 55, smoking cigarettes is a risk factor for heart disease, and for women also if they’ve had certain complications in pregnancy, such as preeclampsia or a severe form of hypertension in pregnancy – we’re learning that they may convey a risk for heart disease down the line.
Graziosi: For further information on the Heart Truth Campaign visit www.hearttruth.gov. This is Cherry Graziosi, The National Institutes of Health, Bethesda, Maryland.
Balintfy: Coming up, a decade of Alzheimer’s disease research—what advances have been made. That’s next on NIH Research Radio.
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A decade of Alzheimer’s disease research
Balintfy: In this special NIH Research Radio interview, we’re talking with Dr. Marcelle Morrison-Bogorad, the former director of the Division of Neuroscience at the National Institute on Aging. She has devoted much of her scientific career to unraveling the mysteries of the aging brain, and age-related neurodegenerative diseases. Having recently retired, she shares her perspective on Alzheimer’s disease research. So Dr. Morrison-Bogorad, how did you get started in science?
Morrison-Bogorad: Well, I went to a very snooty private girl’s school and we were all supposed to end up being wives and mothers, but we had a very feisty science teacher who turned several of us in the direction of science. And I remember one day she was saying, “You know, science is wonderful, but if I had to do my life again, I would study the brain because it's just the most amazing organ in the body.” And that stuck with me.
Balintfy: And was it Alzheimer's disease in particular where you got your start?
Morrison-Bogorad: No, I actually started working on brain development and that was very interesting for a number of years. I had a colleague who studied the development of the cerebellum and we worked together on that for many years. But we -- she and I went to a meeting of the Alzheimer's Association. And I remember meeting this couple and the wife introduced her husband and the husband looked just normal, except when you looked in his eyes and there was nothing there. He had Alzheimer's disease. And Sue Griffin [spelled phonetically], my colleague, and I realized that this was something that really, really needed to be studied. How does the brain change in aging? And how does it change when it's afflicted with a disease like Alzheimer's disease? And how can you have a person who is walking normally and eating and sitting and listening, or at least appearing to listen, and someone who simply is not there anymore? That was really, really quite dumbfounding.
Balintfy: And what did the scientific community know about Alzheimer's disease then as compared to now?
Morrison-Bogorad: You know, this was back in the 1980s and at that time, Alzheimer's disease really was at the beginning of people realizing that it was a disease that occurred in aging people. Some of the major manifestations of it were known already, the plaques and tangles in the brain. But no one knew very much about them.
And so if you consider what's known now with what's known then, I mean, the scientific progress and understanding this complicated disease of the most complicated organ in the body and mixing that with what happens when we grow old when we age, which no one knew very much about back then either, and now we know much more about that as well.
So I think it's been truly astounding, the sort of progress that's been made.
Balintfy: Has Alzheimer’s disease research been challenging?
Morrison-Bogorad: When you're looking at Alzheimer's disease, which is a disease which occurs in the aging body, the aging mind, and you don't really know that much even now about how the mind functions. It's like a car mechanic looking at a car and trying to find out why the engine has died when they don't know how the engine works. It would be like me looking inside a car, in fact.
Balintfy: What do we know now about preventing or delaying the onset of Alzheimer's disease?
Morrison-Bogorad: Well, I wish we knew more. I really hoped that in my tenure at NIH that we would end up having a better handle on how to treat Alzheimer's by the time I left. But I don't think we're there yet. I think, we, you've really got three aspects of science. You've got the very basic science where you ask questions about a problem and get answers. And that tells you a lot about how cells function and how the brain functions and how systems work together. Whatever you ask, really, you can get an answer to a question.
And translational science tries to take what's known about basic science and say, “Okay, if you know that this pathway is affected by this disease, perhaps if you develop a drug that blocks that pathway, you can stop the disease progressing.” So, translational research takes the basic science that we know and tries, in a very practical way, to develop drugs that could work in the clinic.
And obviously, the third and very important part of this is testing drugs that are developed in the translational research part in clinical trials.
So I think one of the things that's happened is that we know so much more in basic science. Every basic science development has the potential for a translational touch to it and through our translational research program at NIA, we now have perhaps 50 or 60 drugs that are being developed that target different aspects of what goes wrong in the brain of a person with Alzheimer's. And we're hoping with such a broad spread, with such a variety of targets that are being developed, that one of them, two of them, three of them, several of them will be good enough to go into clinical trials and actually will stop this disease.
We've got a number of possibilities in the pipeline, but both NIH research and clinical trials and that of the drug companies which, of course, are putting a lot of money into clinical trials. None of us have come up with a clinical trial yet that works and that's the most frustrating thing about the job. It's the most frustrating thing that people who work on Alzheimer's disease face, that we know so much more about the disease, that we have various insights about how to treat it—many more than we use to—but we are still at a loss about how to treat a patient who comes into a doctor's office and who is diagnosed with Alzheimer's.
Balintfy: But are there highlights, things you’re proud of?
Morrison-Bogorad: Oh, yes. I don't want in the least to say that we're not proud. I think we're very proud. When I came to the National Institute on Aging, we had already a number of programs set up where people really -- scientists really worked together to try to solve problems and I think that's been one of the things that I'm most proud of in my tenure. I'm most proud of the scientists working in the Alzheimer's field, that people really have come together in the spirit of collaboration rather than competition to work on this disease and there are several major examples of that. And perhaps one of the most striking recent ones is a collaboration on the genetics of Alzheimer's disease, because Alzheimer's disease has an early onset and a late onset form. We've known the genes that are mutated that cause early onset disease and only one gene which is a risk factor for late onset disease, the most common form of the disease, had been around for a number of years. And people have spent vast amounts of energy and money looking for the other genes.
We, at—in the Division of Neuroscience, decided to bring together all the geneticists in the U.S. and tell them a new technique called GWAS was just being introduced, where you look at the genes, the DNA from thousands of different people and you compare the DNA of normals to the DNA of people who have Alzheimer's disease. And from these thousands of people and lots of computer time, you can identify changes in the genome which are risk factors for developing the disease. But, it needs thousands of people to work on. So we told the geneticists, “You know, you've each got your hundreds of people that you're working on, but you're not going to get very far with that. You need to merge together. You need to form a consortia and make your hundreds, thousands and then you'll be able to get somewhere.”
So we persuaded them to do so. And they are really doing something extraordinary. I’m just very proud of that.
Balintfy: Thank you very much Dr. Marcelle Morrison-Bogorad. We’ll have more about the advances in Alzheimer’s disease research in out next episode:
Morrison-Bogorad: Wouldn't it be wonderful if you could exercise it away?
Balintfy: That and much more next time. For now, that’s it for this episode of NIH Research Radio. Please join us again on Friday, March 11 when our next edition will be available. If you have any questions or comments about this program, or have story suggestions for a future episode, please let me know. Best to reach me by email—my address is firstname.lastname@example.org. I'm your host, Joe Balintfy. Thanks for listening.
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