BreakThrough Digest Medical News |
- Taking cholesterol-lowering drugs may also reduce the risk of dying from prostate cancer: Study
- New molecule heralds hope for muscular dystrophy treatment
- 1 step closer to a blood test for Alzheimer’s
| Taking cholesterol-lowering drugs may also reduce the risk of dying from prostate cancer: Study Posted: 30 Apr 2013 09:00 PM PDT Men with prostate cancer who take cholesterol-lowering drugs called statins are significantly less likely to die from their cancer than men who don’t take such medication, according to study led by researchers at Fred Hutchinson Cancer Research Center. The findings are published online today in The Prostate.
The study, led by Janet L. Stanford, Ph.D., co-director of the Prostate Cancer Research Program and a member of the Hutchinson Center’s Public Health Sciences Division, followed about 1,000 Seattle-area prostate cancer patients. Approximately 30 percent of the study participants reported using statin drugs to control their cholesterol. After a mean follow-up of almost eight years, the researchers found that the risk of death from prostate cancer among statin users was 1 percent as compared to 5 percent for nonusers. “If the results of our study are validated in other patient cohorts with extended follow-up for cause-specific death, an intervention trial of statin drugs in prostate cancer patients may be justified,” Stanford said. “While statin drugs are relatively well tolerated with a low frequency of serious side effects, they cannot be recommended for the prevention of prostate cancer-related death until a preventive effect on mortality from prostate cancer has been demonstrated in a large, randomized, placebo-controlled clinical trial,” said first author Milan S. Geybels, M.Sc., formerly a researcher in Stanford’s group who is now based at Maastricht University in The Netherlands. The study is unique in that most prior research of the impact of statin use on prostate cancer outcomes has focused on biochemical recurrence ? a rising PSA level ? and not prostate cancer-specific mortality. “Very few studies of statin use in relation to death from prostate cancer have been conducted, possibly because such analyses require much longer follow-up for the assessment of this prostate cancer outcome,” Geybels said. The potential biological explanation behind the association between statin use and decreased mortality from prostate cancer may be related to cholesterol- and non-cholesterol-mediated mechanisms. An example of the former: When cholesterol is incorporated into cell membranes, these “cholesterol-rich domains” play a key role in controlling pathways associated with survival of prostate cancer cells. An example of the latter: Statin drugs inhibit an essential precursor to cholesterol production called mevalonate. Lower levels of mevalonate may reduce the risk of fatal prostate cancer. “Prostate cancer is an interesting disease for which secondary prevention, or preventing poor long-term patient outcomes, should be considered because it is the most common cancer among men in developed countries and the second leading cause of cancer-related deaths,” Geybels said. “While many prostate cancer patients have indolent, slow-growing tumors, others have aggressive tumors that may recur or progress to a life-threatening disease despite initial therapy with radiation or surgery. Therefore, any compound that could stop or slow the progression of prostate cancer would be beneficial,” he said. ### The National Cancer Institute, a grant from the Dutch Cancer Society and additional support from Fred Hutchinson Cancer Research Center and the Prostate Cancer Foundation funded the research. At Fred Hutchinson Cancer Research Center, home to three Nobel laureates, interdisciplinary teams of world-renowned scientists seek new and innovative ways to prevent, diagnose and treat cancer, HIV/AIDS and other life-threatening diseases. Fred Hutch’s pioneering work in bone marrow transplantation led to the development of immunotherapy, which harnesses the power of the immune system to treat cancer with minimal side effects. An independent, nonprofit research institute based in Seattle, Fred Hutch houses the nation’s first and largest cancer prevention research program, as well as the clinical coordinating center of the Women’s Health Initiative and the international headquarters of the HIV Vaccine Trials Network. Private contributions are essential for enabling Fred Hutch scientists to explore novel research opportunities that lead to important medical breakthroughs. For more information visit http://www.fredhutch.org or follow Fred Hutch on Facebook, Twitter or YouTube. Contact: Kristen Woodward |
| New molecule heralds hope for muscular dystrophy treatment Posted: 30 Apr 2013 09:00 PM PDT There’s hope for patients with myotonic dystrophy. A new small molecule developed by researchers at the University of Illinois has been shown to break up the protein-RNA clusters that cause the disease in living human cells, an important first step toward developing a pharmaceutical treatment for the as-yet untreatable disease.
Steven C. Zimmerman, the Roger Adams Professor of Chemistry at the U. of I., led the group in developing and demonstrating the compound. The National Institutes of Health supported the work published in the journal ACS Chemical Biology. Myotonic dystrophy type 1 is the most common form of muscular dystrophy in adults, affecting one in 8,000 people in North America. It causes progressive weakness as the muscles deteriorate over time. There is no treatment available for the disease; though a few measures can help ease some symptoms, nothing can halt their inevitable progression. “This is a disease that currently doesn’t have any treatment, so we have a huge interest in finding therapeutic agents,” said graduate student Amin Haghighat Jahromi, the first author of the paper. Myotonic dystrophy type 1, called DM1 for short, is caused by a mutation to one gene. In a healthy person, one small segment of the gene ? a DNA sequence of CTG ? is repeated a few times. In someone with DM1, the sequence is repeated more than 50 times, even up to thousands of repeats. The sequence is transcribed into RNA over and over, like a skipping record stuck in a loop. The repetitive RNA binds to the protein MBNL1, which is essential for regulating protein balance in cells. The RNA traps the MBNL1 protein in aggregates within the cell’s nucleus. “The RNA is functioning in an abnormal way, and unfortunately, it’s toxic,” Zimmerman said. “MNBL regulates a process called alternative splicing that controls how much of different proteins are made. Affected cells make the proteins, just not at the right levels, so all the levels are imbalanced. There are more than 100 proteins that are affected.” The Illinois group developed a small molecule that could infiltrate the nucleus and bind to the RNA, forcing it to let go of MBNL1 so the protein can do its job. The molecule is small and water-soluble so it can cross the membrane into the cell, which has been a challenge for researchers attempting to use methods with larger molecules. It specifically targets only the repeating RNA sequence so as not to interfere with other cellular functions. The researchers administered the molecule to live cells that have the disease features of DM1. Using advanced microscopy methods, they were able to watch the cells over time to see how they responded to the molecule. In only a few hours, they saw the clusters within the nucleus break up and were able to measure that the MBNL1 protein had increased its regulatory activity. “This is the first study that gives direct evidence for the function of the compound,” Jahromi said. “We track how the cell is changing upon treatment with the compound and see the effect directly.” Next, the researchers plan to begin collaborating with other groups to test their molecule in fruit flies and mice. Although the molecule will need many rounds of testing for toxicity, efficacy, metabolism and possible side effects before human trials can begin, finding a molecule that works in living cells is an important first step toward making a drug that could treat myotonic dystrophy. “We’re close to developing drug candidates that can be tested in animals. And if it works in animals, then we move hopefully into clinical trials with humans,” Zimmerman said. “It’s heartbreaking, at one level, to say we’re years away from something that’s going to be in the clinic. On the other hand, we now have targets. We now know how to go after this disease. It gives patients and their families a bit of hope.” ### Editor’s note:
To reach Steven C. Zimmerman, call 217-333-6655; email sczimmer@illinois.edu. A proof version of the paper, “A Novel CUGexp·MBNL1 Inhibitor With Therapeutic Potential for Myotonic Dystrophy Type 1,” is available online. Contact: Liz Ahlberg |
| 1 step closer to a blood test for Alzheimer’s Posted: 29 Apr 2013 09:00 PM PDT Australian scientists are much closer to developing a screening test for the early detection of Alzheimer’s disease. They identified blood-based biological markers that are associated with the build up of a toxic protein in the brain which occurs years before symptoms appear and irreversible brain damage has occurred.
“Early detection is critical if we are to make any real difference in the battle against Alzheimer’s, giving those at risk a much better chance of receiving treatment earlier, before it’s too late to do much about it,” said Dr Samantha Burnham from CSIRO’s Preventative Health Flagship. Alzheimer’s is the leading cause of dementia. One quarter of a million Australians currently suffer from dementia and given our ageing population, this is predicted to increase to one million people by 2050. Sophisticated mathematical models were used to analyse data from 273 participants in the Australian Imaging, Biomarkers and Lifestyle study of ageing (AIBL). This identified nine markers that correlate with brain positron emission tomography (PET) imaging measurements of a toxic protein, amyloid beta, which deposits in the brain as plaques early in disease development. “The progressive build up of the toxic protein, amyloid beta, is one of the earliest changes in the brain associated with the development of Alzheimer’s disease,” said Dr Noel Faux, from the Florey Institute for Neuroscience and Mental Health. “A recent study from the AIBL team showed that amyloid beta levels become abnormal about 17 years before dementia symptoms appear. This gives us a much longer time to intervene to try to slow disease progression if we are able to detect cases early.” Dr Burnham adds “We hope our continued research will lead to the development of a low cost, minimally invasive population based screening test for Alzheimer’s.” “A blood test would be the ideal first stage to help identify many more people at risk before a diagnosis is confirmed with cognitive tests and PET imaging or cerebral spinal fluid (CSF) testing.” ### The results have been published in the journal Molecular Psychiatry. Contact: Andreas Kahl |
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