July 24, 2009
NIH Podcast Episode #0089
Balintfy: Welcome to the 89th 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 program, a report on new efforts to combat rare and neglected diseases; also details on dealing with diabetes. But first, a gene has been linked to testicular cancer. That's next on NIH Research Radio.
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Second Gene Linked to Familial Testicular Cancer
Balintfy: Specific variations or mutations in a particular gene can raise a man's risk of familial, or inherited, testicular germ-cell cancer, the most common form of this disease. This is only the second gene to be identified that affects the risk of familial testicular cancer, and the first gene in a key biochemical pathway. Researchers have suspected for years that heredity plays a role in some patients with testicular germ-cell cancer. Now a recent study shows that multiple genes with weaker individual effects — but acting together — probably influence an individual’s risk of familial testicular cancer.
Stratakis: It appears that this particular tumor, like many other tumors in young adults, has a strong genetic component.
Balintfy: Dr. Constantine Stratakis is with the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
Stratakis: Investigators believe that there is a lot of genetic factors that play a role together in increasing somebody’s risk for developing testicular cancer.
Balintfy: Men with a family member who had a testicular germ cell cancer have greater risk than other men of developing testicular cancer. Although a family history probably accounts for less than five percent of all testicular cancers, the careful study of rare familial cancer clusters has often led to important new understanding of the non-familial versions of the same cancer.
Stratakis: So the key finding here is that we found inactivating mutations in a gene that regulates cyclic AMP levels. Cyclic AMP is a Cyclic nucleotide that is involved in signaling. It mediates the affects of many of the hormones that regulate testicular function.
Balintfy: Dr. Stratakis says Cyclic AMP is one of the most ancient signaling pathways that regulates how cells respond to hormones. It regulates practically everything from cell growth and proliferation to cell metabolism and function.
Stratakis: The role of Cyclic AMP signaling in testicular function and growth has been known for years. But this is the first time that mutations in a gene that regulate the Cyclic AMP levels were linked to a risk for a tumor.
Balintfy: The researchers found that seven different mutations in a specific gene, created abnormal versions of an enzyme that slowed down the enzyme’s destruction of cyclic AMP. But Dr. Stratakis adds, the mutations don’t cause cancer directly, but instead appear to increase an individual’s susceptibility to developing a tumor.
Stratakis: It has been said that we all carry anywhere from 7 to 10 mutations in important genes; we don’t necessarily have disease as a result of these mutations, but we are carriers of mutations of potentially giving us disease.
Balintfy: To conduct the research for this study, Stratakis and his colleagues analyzed the portion of the DNA from 95 familial testicular cancer patients that contains the gene PDE11A. He says learning how disruptions in the PDE11A enzyme lead to an increased risk of tumor formation may help researchers identify other proteins that also play a role.
NIH Announces New Program to Develop Therapeutics for Rare and Neglected Diseases
Balintfy: The National Institutes of Health is launching its first drug development pipeline to produce new treatments for rare and neglected diseases. With a new program specifically intended to stimulate research collaborations, NIH is hoping to take the risk out of making drugs that are often less profitable. Indrani Datta brings us this report.
Datta: More than 25 million Americans suffer from rare diseases.
Guttmacher: And millions of people who have diseases for which there’s no effective therapy today.
Datta: Dr. Alan Guttmacher is the acting director of the National Human Genome Research Institute.
Guttmacher: What we’re trying to do is develop new effective therapies for both rare diseases and so-called neglected diseases.
Datta: Neglected diseases are often common in some parts of the world where people cannot afford or otherwise access treatments, if they exist at all. One example of a neglected disease is malaria, a tropical disease carried by mosquitoes that affects over 300-million people worldwide. A rare disease is a disease that affects fewer than 200-thousand Americans. Cystic fibrosis is one example, affecting the respiratory and digestive systems; another example is Huntington’s disease, which affects the brain and nervous system.
Guttmacher: We’re not going to be able to develop therapies for all 7,000 rare diseases in one fell swoop. But we’re going to both tackle a number of those diseases and come up with processes that we hope others can apply to finding new effective drugs for rare diseases.
Datta: Dr. Guttmacher explains that a 24-million dollar program, called Therapeutics for Rare and Neglected Diseases, plans to bridge the gap between initial drug discovery and patient use.
Guttmacher: There exists a gap today between the early part of the scientific research needed to develop drugs to the clinical trials that are eventually done.
Datta: Typically, drug development begins when academic researchers studying the cause of a disease discover a new molecule or chemical that may have a beneficial effect. Too often, the process gets stuck there because few academic researchers can conduct all the types of studies needed to develop a new drug. If a drug company with resources to advance the research does get involved, substantial preclinical work begins.
Guttmacher: The steps called medicinal chemistry, some toxicology testing, those kinds of things, move the potential drug candidates farther along the pipeline so that they can then be used in clinical trials.
Datta: Only if preclinical work is successful can a potential treatment move to clinical trials in patients. Unfortunately, preclinical success rates are low, with 80 to 90 percent of projects failing. And the costs are high: it takes two to four years of work and roughly 10 million dollars to move a potential medicine though this process.
Guttmacher: It’s referred to in the pharmaceutical industry as the Valley of Death, because it’s where many promising new drugs go to die.
Datta: The Therapeutics for Rare and Neglected Diseases program will work closely with disease-specific experts on selected projects. Dr. Guttmacher adds the entire process itself is going to be examined closely.
Guttmacher: So we’re going to focus on rare and neglected diseases and try to cross this Valley of Death to do the kinds of steps that are necessary. And to improve the way those steps are done compared to how they’ve been done traditionally. To make them shorter steps, to make them less expensive steps so we can really develop new therapies for these rare and neglected diseases.
Datta: Dr. Guttmacher says it will be a few years before the first drugs emerge from this program.
Guttmacher: But we hope that once they do start emerging, it’ll be a steady stream of drugs emerging from it.
Datta: Of the thousands of rare and neglected diseases, only a few will be studied each year. The Therapeutics for Rare and Neglected Diseases program aims to collaborate with academic researchers, patient advocacy organizations, disease-oriented foundations, and private pharmaceutical companies – whatever is needed to get new drugs through clinical trials and to patients. For more information on the program, visit rarediseases.info.nih.gov/TRND. This is Indrani Datta, National Institutes of Health, Bethesda, Maryland.
Balintfy: Coming up after this break, details from an NIH director on dealing with diabetes. Don’t go away.
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Ask Your Health Care Team About Your Type 2 Diabetes – Part II
Balintfy: People with type 2 diabetes are faced with a serious disease that can lead to problems such as heart attack, stroke, blindness, kidney failure and lower limb amputations. In fact, as we heard in a report last episode, heart disease is the number one cause of death for people with diabetes and two out of three people with diabetes die from heart disease or stroke. In this extra interview, we get more details on type 2 diabetes from Dr. Griffin Rodgers, Director of the National Institute of Diabetes and Digestive and Kidney Diseases. So Dr. Rogers, what are the diabetes ABCs?
Rodgers: Well, the ABCs of diabetes are three critical items; the A stands for the hemoglobin, the A1c, and that’s a general measure of the average glucose or sugar control in the preceding two to three months. Typically, for most patients, we like that A1C value to be less than seven percent. The B stands for blood pressure, and for most patients with type-II diabetes, a target for that blood pressure should be less than 130/80. C stands for cholesterol, or the so-called bad cholesterol, or LDL cholesterol, we typically like that target to be 90 or less.
Balintfy: Are there questions people should ask their health care team about the diabetes ABCs?
Rodgers: Sure, the critical fact, with the questions, when one has an opportunity to speak to their health care provider is really to ask them, “What are the goals?” and “How am I along the path to achieving those goals?” And that again relates to the A1C, the blood pressure, the cholesterol, the level of intensity of physical activity that one participates in, as well as one’s diet plan.
Balintfy: What are examples of goals that people can set to help them manage their diabetes?
Rodgers: I think it's very important to pick a realistic goal, and something that one can stick with, and set that goal, write it down, and then work toward that goal. So for example, if your goal is to increase your physical activity, pick an activity that would be realistic for you, such as walking for example, and plan to walk for a certain number of minutes a day. And depending on how active you’ve been before; if you’ve not been very active, one might start with 15 minutes, and then gradually elevate that level of activity. A second goal might be related to, perhaps, changing one’s diet. One might be able to best accomplish that by diminishing the portion sizes that one has, and so considering that first, and then cutting back on calories and the content of fats, for example, might be a realistic goal to consider. The third thing of course, and these aren’t mutually exclusive, is to consider the medications that you’re taking. If you are taking medicines for your diabetes, and if your hemoglobin A1C isn’t in the normal range that your health care provider has set for you, then bring in either your monitor or your log of your blood sugar levels and work with your health care provider to either adjust your medication, or the combination and balance of your medications, your diet, and your physical activity.
Balintfy: How often should people with type 2 diabetes visit their health care team?
Rodgers: In general we think that patients should have at least two visits with their health care provider over the course of the year, at which point the hemoglobin A1 C should be measured. So again, we suggest that for the average patient there should be at least two of these readings. Of course, at this opportunity, on an annual basis, we want to make sure that the blood pressure is checked, the cholesterol and particularly the LDL level is checked. Having an eye examination is critically important, because as I mentioned, eye disease is an important complication. And this also gives the health care provider an opportunity to screen for kidney damage, and testing the blood as well as the urine for evidence of what we call diabetic nephropathy. So those are critical reasons to see a health care provider, and to get these done, certainly on a twice a year basis. Of course, now, if there are complications associated with their disease, the health care provider may want to structure even more frequent visits.
Balintfy: Are there other tests people with type 2 diabetes should ask their health care team about?
Rodgers: Well, in addition to the tests that I’ve mentioned, of course, it’s important to have, at least on an annual basis, this dilated eye examination, so one could look for the presence of diabetic retinopathy. In addition, of course, we’re looking for evidence of kidney damage, so a urine and a blood test to look for so-called diabetic nephropathy is important. Looking for evidence of disease in the foot, and so a foot examination, using fibers to examine the touch and feeling sensation there is a good way to look for nerve damage that might accompany diabetes as it relates. Hopefully we’ll prevent patients going on for requiring amputations in their feet.
Balintfy: More information on managing type 2 diabetes is available in the brochure called “4 Steps to Control Your Diabetes. For Life.” It is available through the National Diabetes Education Program. Call 1-888-693-NDEP or visit www.yourdiabetesinfo.org. And if you’d like to see this interview with Dr. Rodgers, check out the NIH vodcast, I on NIH. The interview is featured in episode 22 and will also be up on the NIHOD channel of YouTube.
Balintfy: That’s it for this episode of the NIH Research Radio podcast. Please join us again on Friday, August 7 when our next edition will be available for download. 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.