November 27, 2009
NIH Podcast Episode #0098
Balintfy: Welcome to the 98th episode 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. Coming up in this episode, how one of the nation’s largest American Indian tribes, is working to curb the rapid rise of smoking rates in its community. Also, an in-depth discussion with two physician researchers about rare, genetic immune deficiency diseases plus where they’re being treated. But first, news about genetic discoveries and Parkinson’s Disease. That's next on NIH Research Radio.
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[PSA: Happy Holidays from the NIH Research Radio podcast! A couple holiday and anniversary notes for you: we’re skipping a week for Christmas. Episode 99 stays on schedule, but after that the next edition will be available for download on Friday, January 1st, not December 25th. January 1, 2010 marks the 100th anniversary when we’ll re-launch with new features, and continue every two weeks from then. Be sure to keep tuning in. Thanks for listening and Happy Holidays again from NIH Research Radio!]
Researchers Identify Gene Mutations Underlying Risk for Most Common Form of Parkinson's Disease
Balintfy: Researchers have found that two genes containing mutations known to cause rare familial forms of Parkinson’s disease are also associated with the more common form of the disease where there is no family history. Collaborating scientists in the United States and Europe pooled nearly 14,000 DNA samples and data to confirm the mutations in specific genes, and associated proteins—both which are present in the general population—are risk factors for Parkinson's disease. Dr. Andrew Singleton, chief of the Laboratory of Neurogenetics at the National Institute on Aging, explains, scientists have already identified five genes whose rare mutations cause the disease.
Dr. Singleton: What we found with this latest study, is that two, and possibly three of those genes, also contained common variants that you or I have a very high chance of carrying, they’re present in 20 or 30 percent of the population. So these common variants increase our risk.
Balintfy: But Dr. Singleton is quick to add that these genetic mutations don’t cause Parkinson’s disease. Rather these variations add to the risk by a small amount, only about 20-30 percent.
Dr. Singleton: A good way to conceptualize this is that if you were to take a hundred people from the general population on average, about one of those would get Parkinson’s Disease. And if you were to take a hundred people from the general population, who all carried the risk variants that we found, about one or about two people would, from that population, would get disease. So, it’s a fairly moderate increase in risk for disease.
Balintfy: Parkinson's disease is a progressive neurologic disorder caused by the degeneration of nerve cells in the portion of the brain that controls movement. The likelihood of developing the disorder increases with age and involves a combination of environmental risk factors and genetic susceptibility. Dr. Singleton says there are about one million people in North America affected with Parkinson’s disease.
Dr. Singleton: But of course, given that the population is aging, we’re all aging a bit more successfully and everybody’s living a little bit longer, there will be more people affected with Parkinson’s Disease over the next 10 or 20 years.
Balintfy: Because of the potential increase in cases, Dr. Singleton says these findings, presented in a recent online issue of Nature Genetics, are important to help understand the disease.
Dr. Singleton: So, I don’t see immediate use for this in identifying people who are going to get disease or providing risk profiles for people, I think we will get there, but that’s a ways off yet. What it really tells us is that the genes that we’ve identified are intimately involved in the process that leads to Parkinson’s disease, so it really gives us an in to understanding what are the molecular events that lead to disease, and of course once we know that, we’re one step closer to trying to find a point in that process to halt the disease or to reverse the disease process.
Balintfy: The finding came in the largest genome-wide association study reported to date involving Parkinson's disease. Genome-wide association studies look in the DNA of individuals in a specific population for common genetic associations with a disease. To date, such studies have been done on relatively small numbers of samples and have not been able to identify genetic variations of smaller effect in Parkinson's disease. But now, genome-wide association studies in very large sample sets are able to identify these elusive genetic variations. For more information on this study, visit www.nia.nih.gov.
Striving for a Smoke Free Navajo Nation
Balintfy: November is National Native American Heritage Month. Just in time Kristine Crane brings us this report: we learn how policy makers on the Navajo Nation, the country’s largest American Indian tribe, want to enforce tobacco free legislation to curb the rapid rise of smoking that has occurred in the Nation during the past two decades.
Crane: Smoking rates have increased rapidly on the nation’s Indian reservations in the past two decades.
Dr. Nez Henderson: Navajo Nation historically had very low rates of smoking.
Crane: Dr. Patricia Nez Henderson is the Vice President of the Black Hills Center for American Indian Health, a non-profit health organization in Rapid City, South Dakota.
Dr. Nez Henderson: The rates of smoking now among the young adult population hovers around about forty percent.
Crane: The Navajo Nation, which includes parts of Utah, Arizona and New Mexico, is a sovereign nation that sets its own policies for tobacco control.
Dr. Nez Henderson: We are currently working with the Navajo Nation in passing a comprehensive tobacco-free policy for the nation. It would prohibit the use of commercial tobacco in all public places, places of employment as well as private vehicles with children under the age of eighteen.
Crane: Dr. Nez Henderson hopes the recently passed Family Smoking Prevention and Tobacco Control Act will help curb smoking in the Navajo Nation. But she adds that tribal healers also must be convinced to discontinue using tobacco in their practices.
Dr. Nez Henderson: Historically traditional healers use natural plants and herbs for their own ceremonial practices, but because of access and many other issues they’re beginning to use and have used commercial tobacco for their ceremonies. So now it’s just going back into these communities and educating these traditional healers that however you use commercial tobacco, it is deadly and harmful, and that’s the message that we’re giving to our leaders.
Crane: Dr. Nez Henderson spoke as part of the ninth NIH American Indian and Alaska Native Heritage Month Program. For more information on Native American health, visit www.americanindianhealth.nlm.nih.gov. This is Kristine Crane, the National Institutes of Health, Bethesda, Maryland.
Balintfy: Coming up next, Primary Immune Deficiency Diseases, their genetic roots and a place of treatment. Stay tuned, we’ll be back after this announcement.
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Scientists Identify Genetic Cause of Previously Undefined Primary Immune Deficiency Disease
Balintfy: Researchers at the National Institutes of Health have identified a genetic mutation that accounts for a perplexing condition found in people with an inherited immunodeficiency. The disorder, called combined immunodeficiency, is characterized by a range of severe health problems, including persistent bacterial and viral skin infections, severe eczema, acute allergies and asthma, and cancer. Combined immunodeficiency is a type of primary immune deficiency disease in which several parts of the immune system are affected. To learn more about this inherited disorder and the primary immune deficiency disease clinic, I had a discussion with Drs. Helen Su and Gulbu Uzel both with the National Institute of Allergy and Infectious Diseases. I started with Dr. Uzel, to get an understanding of what primary immunodeficiency diseases are.
Dr. Uzel: Primary immunodeficiency diseases are the diseases that you are born with. It’s genetically dictated, and that those are the diseases that predispose you to infections, the sort of infections that do not affect other healthy people, but affects either more frequently or in different ways people that are affected with or born with these primary immunodeficiency diseases.
Balintfy: Dr. Uzel, because these are diseases that people are born with, does that mean they affect children more than adults?
Dr. Uzel: It can affect anyone, but usually it manifests itself—the primary immunodeficiencies manifest themselves early on in life, so that’s why a majority of our patients are kids. That’s where the incidence is much higher in terms of diagnosis.
Balintfy: Are primary immunodeficiencies rare?
Dr. Uzel: In the United States, one in every—I guess one in every 500 people have a form of immunodeficiency, it’s estimated. It’s a very high number, but people argue about that incidence back and forth.
Balintfy: Dr. Su, do many with these kinds of diseases go undiagnosed?
Dr. Su: There’s probably an under-appreciation/under-estimation of the actual incidence in the population. People will often attribute, "Oh, you know, that person gets sick a lot," but it’s not enough to land them in the hospital and be in the hospital for months or weeks. So then people will say, you know, "that’s normal" and they may sort of not pay attention to it, especially in some parts of the country where the physicians might not be as in tune with the possibility there might be a problem with the immune system.
Balintfy: Are there examples that you could share that might be easily understandable or identifiable as a primary immunodeficiency disease. Dr. Uzel?
Dr. Uzel: The one that everybody knows is the "bubble boy." The story of the "bubble boy," which is actually Severe Combined Immunodeficiency, that’s one of the most severe and worst of all immunodeficiencies. And unless the patient is given a new healthy bone marrow from a healthy donor, patients don’t survive. So that’s one end of the spectrum. But then there’s the other end of the spectrum where as you get older during your adulthood, late teenager or early adult years, you can develop—lose your immunoglobulins and get diagnosed with Common Variable Immunodeficiency. You get infections, sinus infections, lung infections and can be maintained with immunoglobulin infusions, so that’s the other end of the spectrum. In between the two, there are a lot of different types of immunodeficiency disorders. Each one comes with a different set of problems.
Dr. Su: Well, the most common symptomatic primary immunodeficiency affecting adults is Common Variable Immunodeficiency, which is estimated to be one in about 20,000 individuals; some of the other ones which are much rarer, one in a million, one in two million.
Balintfy: Dr. Su, now recently, your team made a discovery about a previously undefined primary immune deficiency. Can you explain how this happened?
Dr. Su: Well, this discovery was made in a group of patients, but they were a group of patients that didn’t quite fit any known diagnosis very well. I mean, the disease that was most often compared to them was something called hyper-IgE syndrome, and they present with a lot of IgE, which is a type of antibody in the blood that normally is not very high. And those patients tend to have a lot of skin infections, but this particular group of patients that we were looking at had some unusual features which weren’t shared by those patients, and that included severe allergies to foods and really unusual viral infections of the skin that were quite severe. And you could find them in normal people but not to the degree that these patients had, and Gulbu can talk more about that.
Dr. Uzel: So we truly believe in the accidents of nature, and this was an accident of nature because the way this discovery was made was with the help of this little girl, and since both of her parents were carriers for this disease—but, of course, carriers are not clinically symptomatic, she was affected because of missing a big chunk of the gene in both copies—both copies, both alleles—Dr. Su with her technique was able to pick up a missing signal in the DNA. And when she made that discovery, we looked at what other patients we have similar to this patient that share some clinical features. So she did these similar studies with patients with the similar clinical features and was able to identify mutations. So now her mutation was a big—the reason that it was very helpful and I call it an accident of nature, is because it was a big chunk deleted. None of the other patients had, I guess, in both—but not, I mean, she was just leading—very clear, that’s true.
Dr. Su: It was like there was a big arrow saying, "This is the gene you need to look at because it’s missing in me." That’s what her DNA showed.
Dr. Uzel: That’s how it worked.
Balintfy: Is the NIH Primary Immune Deficiency Disease clinic a resource for others who might have these kinds of diseases?
Dr. Uzel: That’s certainly a possibility. We serve as a referral center, meaning we would like the patients to be referred by their physicians or by their immunologist, where we do a lot of center-to-center referral. And we like to serve as a resource rather than acting the, in most cases, the primary care provider, so that’s one of our prerequisites, that the patients do need to have a primary care provider and be referred by a physician.
Dr. Su: The other thing that we do, which is probably a little bit different, is because we have the ability to really think about these individual patients and about their disease process, we can actually sort of design tests in some regards, research tests to sort of ask what exactly is going on, and so it’s a little bit different aspect from what you might have at a research setting elsewhere.
Dr. Uzel: One thing that I would like to emphasize is the importance of seeing a patient, observing a patient and carrying out the observation and the problem to a research level and investigating the problem on a cellular and genetic level. So a true collaboration between a dedicated clinician and a dedicated scientist is what leads to discovery in this field. And that model is, I think, the ideal model for the 21st century.
Balintfy: Dr. Gulbu Uzel and Dr. Helen Su, thank you very much. For more information on the primary immune deficiency disease clinic and combined immunodeficiency, visit www.niaid.nih.gov.
And that’s it for this episode of NIH Research Radio. Please join us again on Friday, December 11 when our next and last edition for the year will be available for download. Remember, we’re skipping December 25th, but will start up again with our 100th episode on January 1, 2010. For now, until December 11, I'm your host, Joe Balintfy. Thanks for listening.
NIH Research Radio is a presentation of the NIH Radio News Service, part of the News Media Branch, Office of Communications and Public Liaison in the Office of the Director at the National Institutes of Health in Bethesda, Maryland, an agency of the US Department of Health and Human Services.