FDA seeks more controls on combination painkillers. In a significant shift in policy that has implications for laboratory testing, The Food and Drug Administration (FDA) has recommended that much tighter controls be placed on how doctors prescribe the most common narcotic painkillers. The decision to reduce the number of refills of drugs such as Vicodin and Lortab—combination drugs that include both the narcotic hydrocodone and over-the-counter painkillers—comes in the context of a debate that has raged for years over whether control of such drugs should be increased. They would now be regulated in much the same way as more powerful painkillers such as OxyContin.
The FDA proposal would re-classify the combination painkillers as “Schedule II” medications; they are currently classified as “Schedule III.” In addition to limiting the number of refills a patient could get without a follow-up visit to the doctor, the change would require patients to take a prescription to a pharmacy (it could no longer simply be called in by the physician). The new regulations would reduce by half, to 90 days, the supply of the drug a patient could obtain without a new prescription.
Dr. Janet Woodcock, director of the agency’s center for drug evaluation and research, believes that the new regulations could take effect as early as next year. The recommendation requires the approval of the Department of Health and Human Services and adoption by the Drug Enforcement Administration, which has been a vocal proponent of the measure.
Researchers discover how to determine parental origin of a given genetic sequence. A new technique successfully takes on a longstanding challenge in DNA sequencing: determining whether a particular genetic sequence comes from an individual’s mother or father. The method, described in a Ludwig Cancer Research study published in Nature Biotechnology, promises to accelerate studies of how genes contribute to disease, improve the process of matching donors with organs, and help scientists better understand human migration patterns.
“The technique will enable clinicians to better assess a person’s individual risk for disease. It is potentially transformative for personalized medicine,” says Bing Ren, PhD, who led the research on the new technique, called HaploSeq. “Current sequencing technologies are fast and rapidly getting cheaper; an individual’s genome can now be sequenced in about a week for $5,000. In the not-too-distant future, everyone’s genome will be sequenced. That will become the standard of care.”
However, Ren explains, “There has been a problem with this scenario.” Except for the sex chromosomes, everyone has two copies of each chromosome. One comes from mom, and the other from dad.Current techniques cannot distinguish between the two copies of each gene and thus are not very good at determining whether particular genetic differences, such as a single-letter change in the DNA, originate with an individual’s mother or father.
The new technique, which mixes molecular biology and computational biology approaches, bypasses this problem. The method enables researchers to quickly determine which genetic variants occur together on the same stretch of chromosome and, therefore, came from the same parent. It allows clinicians to better assess a person’s individual risk for disease, a cornerstone of personalized medicine.
Study links mutations to breast cancer treatment resistance. In a study published online in Nature Genetics, researchers at the University of Michigan have identified a type of mutation that develops after breast cancer patients take anti-estrogen therapies. The mutations suggest one reason why patients often become resistant to this therapy. The discovery stems from a program at the U-M Comprehensive Cancer Center, called Mi-ONCOSEQ, in which patients with advanced cancer have their DNA and RNA sequenced to identify all types of genetic mutations that could play a role in the cancer. Researchers use the findings to help direct therapies they think will work best. But they also use the data to find new genetic links. The detailed analysis means that researchers can identify anomalies among a small number of patients.
In this case, they looked at 11 patients with metastatic breast cancer that was classified as estrogen receptor-positive, meaning the cancer is influenced by estrogen. The analysis found that six patients had mutations in the estrogen receptor. All had been treated with an aromatase inhibitor, a type of drug that blocks estrogen production. The researchers found that the mutations were not present before the patients started their treatment; it was the therapy itself that caused the mutations to develop or be selected.
“This is the tumor’s way of evading hormonal therapy. These mutations activate the estrogen receptor when there is no estrogen—as is the case when a patient takes an aromatase inhibitor,” says lead study author Dan Robinson, PhD. Robinson and colleagues suggest that blood tests could be used to monitor patients and detect these mutations to potentially shift treatment before resistance develops.
A major Alzheimer’s risk factor is linked to resveratrol. The major genetic risk factor for Alzheimer’s disease (AD), present in about two-thirds of people who develop the disease, is ApoE4, the cholesterol-carrying protein that about a quarter of us are born with. But one of the unsolved mysteries of AD is how ApoE4 causes the risk for the disease. In research published in The Proceedings of the National Academy of Sciences, scientists at the Buck Institute for Research on Aging found a link between ApoE4 and SirT1, an “anti-aging protein” that is targeted by resveratrol, which is present in red wine.
The researchers found that ApoE4 causes a dramatic reduction in SirT1, which is one of seven human Sirtuins. The reduction was found both in cultured neural cells and in brain samples from patients with ApoE4 and AD. They also found that abnormalities associated with ApoE4 and AD, such as the creation of phospho-tau and amyloid-beta, could be prevented by increasing SirT1, and have identified drug candidates that exert the same effect.
“This research offers a new type of screen for Alzheimer’s prevention and treatment,” says Rammohan V. Rao, PhD, co-author of the study. He adds, “One of our goals is to identify a safe, non-toxic treatment that could be given to anyone who carries the ApoE4 gene to prevent the development of AD.”
Consulting firm says business priorities may be delaying HIV breakthroughs. Despite the success of antiretroviral therapy (ART) in the treatment of HIV, a number of challenges stand in the way of novel non-ART interventions, says the latest report from the British research and consulting firm GlobalData. The report says there is an ongoing need for interventions to control the HIV pandemic, including prophylactic vaccines, novel salvage therapies, and an eventual cure which will release patients from long-term ART.
Various efforts targeting different aspects of HIV are emerging, such as latency reversal agents and immunotherapies that educate the immune system to eliminate virus-infected cells. GlobalData believes that the success of a functional cure could well come from an intervention which combines these approaches.
Dr. Charalampos Valmas, GlobalData’s analyst covering infectious disease, says, “The need for new combinatorial therapies presents a unique opportunity for small biotech companies and academic laboratories to combine their forces, and we expect that the first successful regimen will attract Big Pharma, which could use its resources to conduct large-scale trials and market the therapy successfully.”
However, Valmas continues, there are significant barriers to new HIV treatments, including the fact that vaccine research and development is not now a priority for large drug companies. “Big Pharma does not consider HIV or other STD vaccines as lucrative as those for airborne diseases, such as influenza, due to the limited patient segments that an HIV vaccine would initially address. As a result, research is instead being conducted by biotech companies and academic and government-funded institutes, which may not possess the financial capabilities to proceed to Phase III trials.” MLO would be pleased to print responses from readers who agree or disagree with GlobalData’s assumptions and conclusions.
IDSA: Better tests needed to improve patient care, public health. Despite advances in diagnostic technology, there is an urgent need for tests that are easy to use, identify the bug causing an infection, and provide results faster than current tests, according to a report from the Infectious Diseases Society of America (IDSA).The report, “Better Tests, Better Care: Improved Diagnostics for Infectious Diseases,” outlines specific recommendations to spur research and development of new diagnostics and to encourage their use in patient care and public health. Specifically, IDSA calls for:
• fiscal incentives and streamlined regulatory pathways to make it financially and logistically viable for companies to perform diagnostics research and development in areas of greatest unmet need;
• improved clinical research infrastructure to accelerate diagnostics development—for example, providing critically needed specimens that researchers and companies can use to make sure their tests provide accurate results;
• funding for outcomes research to demonstrate the clinical value of diagnostic tests, increasing the likelihood they will be used by doctors and hospitals; and
• appropriate reimbursement, additional supporting infrastructure (such as information technology), and education for those who would utilize the diagnostics.
New law in New York will require hospitals to offer HCV testing. Effective Jan.1, a bill passed by the New York state legislature and signed into law by Gov. Andrew M. Cuomo will require hospitals and health service providers to offer testing for the hepatitis C virus (HCV) to all patients born between 1945 and 1965. According to the U.S. Centers for Disease Control and Prevention (CDC), approximately 75% of hepatitis C infection and about 73% of HCV-associated mortality occurs in individuals born during that time span—that is, “baby boomers.” New York State’s Department of Health has released statistics showing that as many as 150,000 New Yorkers are unaware of their HCV status. The new law will ensure that all baby boomers are offered an HCV screening test or diagnostic test whenever they are patients at a hospital, clinic, or physician’s office.