Infectious Disease
CDC urges aggressive perscribing of antivirals to combat flu. In a telebriefing with reporters held on January 9, Centers for Disease Control and Prevention (CDC) head Thomas Frieden, MD, MPH, confirmed what many Americans have observed—that a harsh flu season is underway in the United States. He called 2014-2015 “a bad year for flu, especially for older people and people with underlying health conditions.” According to government statistics, 26 children had died of flu as of early last month, and hospitalizations among patients over 65 had increased significantly. One reason, Frieden indicated, is that the predominant strain this year is the unusually virulent H3N2. Moreover, approximately two-thirds of the observed H3N2 strains were not included in this year’s flu shot.
Dr. Frieden used the forum to urge physicians to prescribe antiviral medications such as Roche’s Tamiflu even before cases are confirmed by laboratory analysis as part of efforts to control the disease. “In the context of an H3N2 predominant season, with a less effective vaccine, treatment with anti-flu drugs is even more important than usual,” he said. There has been considerable debate about the value of the antivirals; the Cochrane Collaboration, an international group formed to review clinical trials, has strongly questioned the efficacy of Tamiflu. One recent Cochrane news release asserts that “there is no good evidence to support claims that it reduces admissions to hospital or complications of influenza.” According to Frieden, however, CDC scientists are satisfied that there is “compelling evidence” that, particularly when used within the first 48 hours of infection, antivirals help to reduce the severity and duration of the flu.
Molecular Diagnostics
AMP releases a white paper describing “A Molecular Diagnostic Perfect Storm.” The Association for Molecular Pathology (AMP), a nonprofit organization serving molecular testing professionals, announced the release of a white paper addressing the consequences of regulatory and reimbursement forces directed against molecular diagnostic testing that the organization says threaten patient care.
“The breakthroughs made possible by mapping the human genome—a multi-billion dollar project that took more than a decade to complete—are being threatened by government regulations, which in turn are threatening patient access to truly revolutionary treatments,” says Victoria M. Pratt, PhD, Indiana University School of Medicine, lead author of the paper. “We hope that this manuscript further enlightens regulatory and reimbursement stakeholders about the storm brewing in Washington that could dismantle the development and coverage of important molecular diagnostic tests.”
Medical professionals in universities, cancer centers, clinical laboratories, and pharmaceutical/manufacturing companies across the country have honored the public trust in the Human Genome Project by developing hundreds of innovative diagnostic tests and therapies that are advancing modern medicine in ways that would have been impossible without this breakthrough. By eliminating the barriers outlined in “The Perfect Storm” paper, genome-based research will continue to play a critical role in the development of more powerful tools to treat complex diseases such as cancer, diabetes, and cardiovascular disease.
The white paper identifies threats stemming from efforts by the U.S. Food and Drug Administration (FDA) and the Centers for Medicare and Medicaid Services (CMS), the two federal agencies that oversee molecular diagnostic testing, as the cause of this “Perfect Storm.”
It argues that the FDA’s new policies will effectively reformulate existing medical device regulations and consider medical professionals as manufacturers, and that this will impose substantially new and duplicative requirements on clinical laboratories and hospitals.
Meanwhile, CMS, whose actions are frequently mimicked in the private sector, has taken what AMP representatives are calling a heavy-handed approach in denying coverage or reducing payment for several medically necessary molecular pathology tests. Healthcare providers—those developing and delivering innovative diagnostic tests—along with patients, who are the ultimate intended beneficiaries, are caught in the middle.
“AMP is addressing the consequences of this gathering perfect storm of regulatory and reimbursement challenges directed against molecular diagnostic testing with recommendations designed to preserve patient access to these essential medical services,” says AMP President Janina Longtine, MD. “We are greatly concerned that these forces are coalescing to bring about consolidation of laboratory testing, to the detriment of local testing. This would have far-reaching negative effects on the healthcare system. As such, AMP is committed to working with the regulatory and reimbursement bodies to find a resolution that optimizes patient safety and offers access to important medical tests.”
“A Molecular Diagnostic Perfect Storm: The Convergence of Regulatory & Reimbursement Forces that Threaten Patient Access to Innovations in Genomic Medicine” is available at http://www.amp.org/publications_resources/position_statements_letters/PerfectStorm.cfm
Genetics/Genomics
Biogen Idec and Columbia University Medical Center will conduct Collaborative Genetics Research. Biogen Idec and Columbia University Medical Center have formed a $30 million strategic alliance to conduct genetics discovery research on the underlying causes of disease and to identify new treatment approaches. As part of this agreement, a sequencing-and-analysis facility will be established at Columbia to support collaborative genetics studies. The agreement will integrate genomics research conducted at Columbia with Biogen Idec’s understanding of disease mechanisms and pathways and expertise in discovering new medicines.
“Our understanding of human genetics is rapidly expanding, and there is growing recognition that the elucidation of the genetic causes of disease will have a transformative effect on both patient care and drug development in many different diseases,” says David Goldstein, PhD, founding director of Columbia University’s Institute for Genomic Medicine. “This collaboration marries the drug development expertise of Biogen with the genomics expertise at Columbia. It will not only focus on target identification and validation at the early stages of drug development, but also facilitate genetically informed evaluation of treatments.”
The new facility will have broad genetic research capabilities and the capacity to launch and complete whole-genome sequencing projects rapidly. It will allow for rapid population-scale DNA sequencing across a broad range of disease areas, focusing on diseases with significant unmet clinical need such as amyotrophic lateral sclerosis (ALS) and idiopathic pulmonary fibrosis.
Cancer
Researchers identify novel breast cancer gene. A new multicenter study has identified a gene that is especially active in aggressive subtypes of breast cancer. The study suggests that an overactive BCL11A gene drives triple-negative breast cancer development and progression. The research, which was done in human cells and in mice, provides new routes to explore targeted treatments for this aggressive tumor type.
There are many types of breast cancers that respond differently to treatments and have different prognoses. Approximately one in five patients is affected by triple-negative breast cancer; these cancers lack three receptor proteins that respond to hormone therapies used for other subtypes of breast cancer. In recent years it has become apparent that the majority of triple-negative tumors are of the basal-like subtype.
Although new treatments are being explored, the prognosis for triple-negative cancer is poorer than for other types. To date, only a handful of genomic aberrations in genes have been associated with the development of triple-negative breast cancer.
The team looked at breast cancers from almost 3,000 patients. Their search had a particular focus: they examined changes to genes that affect the behavior of stem cells and developing tissues, because other work they have done suggests that such genes, when mutated, can often drive cancer development. Among these was BCL11A.
Higher activity of the BCL11A gene was found in approximately eight out of ten patients with basal-like breast cancer and was associated with a more advanced grade of tumor. In cases where additional copies of the BCL11A gene were created in the cancer, the prospects for survival of the patient were diminished. When BCL11A was inactivated in an experimental system in mice, no mice developed tumors in the mammary gland, whereas all untreated animals developed tumors.
Researchers propose that BCL11A is a strong candidate for development of a possible targeted treatment.
Prenatal Testing
New molecular diagnostic methods could reduce risk of miscarriage in prenatal testing for genetic diseases. Early diagnosis and treatment are crucial to improving patient prognosis for 22q11 deletion syndrome and Wilson disease, two potentially life-threatening genetic conditions. Breaking research in the “Molecular Diagnostics” issue of Clinical Chemistry, the journal of AACC, shows for the first time that a more precise technology for quantifying DNA could enable all newborns to be tested for 22q11 deletion syndrome; and that a new method known as cSMART can diagnose a fetus with Wilson disease without the risk of miscarriage that comes with traditional prenatal tests.
22q11 deletion syndrome is considered one of the most common chromosomal deletions associated with birth defects and leads to a wide range of health problems, from heart defects to behavioral disorders. Proposals have been made to include 22q11 deletion syndrome in newborn screening panels so that infants can be diagnosed and treated immediately after birth. The current gold standard method for diagnosing this disorder, however, is too expensive and labor-intensive for screening all newborns.
A team of researchers led by Flora Tassone, PhD, has shown for the first time that a method for quantifying DNA known as droplet digital polymerase chain reaction (ddPCR) can reliably and cost-effectively diagnose 22q11 deletion syndrome. To determine this, the researchers blindly intermixed blood spot cards (the sample form used in newborn screening) from 26 22q11 deletion syndrome patients with 1,096 cards from the general population. Using ddPCR to analyze each sample, they were able to correctly identify the 26 cases of 22q11 deletion syndrome with 100% accuracy and at a cost of only $5 to $6 for reagents per reaction.
Wilson disease results from a mutated version of the gene ATP7B that, when inherited from both parents, causes liver and neurological damage and eventually death. If it is detected and treated early enough, patients with Wilson disease can lead normal lives. Currently, prenatal diagnosis of Wilson disease is performed by analyzing fetal cells collected by either chorionic villus sampling or amniocentesis. Both of these invasive methods come with the risk of complications such as miscarriage, but Wilson and other single-gene disorders like it are difficult to diagnose using safer non-invasive methods—which analyze fetal DNA in the mother’s blood—because the fetal gene of interest is present in the mother’s blood at such low levels.
A research team led by Lingqian Wu, PhD, has developed a new non-invasive prenatal testing method named circulating single-molecule amplification and resequencing technology (cSMART). In a study of four pregnancies where both parents were Wilson disease carriers, the team demonstrated that cSMART can diagnose Wilson disease if the sequences of the parents’ mutant ATP7B variants are known. The researchers used DNA sequencing to determine each couple’s ATP7B variants, then used both standard invasive prenatal testing and cSMART to test for these respective variants in each couple’s fetus. Among the four pregnancies, invasive prenatal testing detected two carrier fetuses who had inherited mutant paternal ATP7B, one unaffected fetus, and one fetus with Wilson disease. cSMART successfully made the same diagnoses.
