Monthly Archives: June 2012

Fake Meg Ryan ad sheds light on celeb drug endorsements

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Adam Levine, frontman of the rock band Maroon 5, has ADHD—a fact he states in awareness ads sponsored by the pharmaceutical company Shire that are sometimes paired with the NBC show “The Voice”, on which he is a judge. Shire is the maker of the ADHD drugs Intuniv (guanfacine) and Vyvanse (lisdexamfetamine). Aided by Levine’s star power (and that of his golden retriever Frankie, who cameos in the spot), Vyvanse is likely to pull in $1 billion this year.

The ad makes Levine the latest in a long line of celebrities who have been on the payroll of pharmaceuticals and appeared in ads. The list famously includes Paula Deen, Bob Dole and Sally Field. Even Larry the Cable—and Prilosec—Guy has gotten in on the action.

In general, consumer pharmaceutical ads (the kind featuring beaming and healthy but unknown faces) are as effective at boosting sales as they are at attracting vitriol. To critics, the use of celebrities only serves to make drug ads more galling. Just look at the Congressional probes, media criticism and other embarrassments they have spurred. But every time the subject bubbles up again (thanks Adam and Frankie!) it seems that one question—having nothing to do with taste or ethics—is overlooked: do celebrities add potency to drug ads?

Well, in March, Health Marketing Quarterly published a study focused on that very question. While the research looks only at print ads, and does not consider the seemingly ubiquitous television counterpart to them (we are looking at you, Sally Field) it provides some interesting data. The researchers created two types of ads for a fictitious antihistamine, unimaginatively dubbed ‘Allergone’. One depicted actress Meg Ryan. The other featured a non-celebrity. They asked 482 adults what they thought. In short, they found, “no significant difference in credibility and effectiveness” between the two ads. So, celebrities may not be very convincing salespeople when it comes to drugs, according to the researchers, lead by Nilesh Bhutada, a pharmacy care administrator at California Northstate University College of Pharmacy in Rancho Cordova, California.

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Key to suicide prevention may lie in subgroup analysis

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If efforts to prevent suicide—a cause of death that takes nearly 1 million lives each year worldwide—are going to be effective, experts may have to look beneath national rates.

Country averages belie the fact that suicide rates often vary widely among socioeconomic and regional subgroups. That revelation comes from an expansive collection of articles, published yesterday in the Lancet, some of which dig into decades worth of data for a deeper understanding of what they call a badly understood, underreported problem.

In Australia, for example, as the nationwide suicide rate fell from 40 per 100,000 in 1997 and 1998, to 20 per 100,000 in 2003, it was rising among young men living in rural and isolated areas, Alexandra Pitman, a population health scientist at University College London, and her colleagues point out in their paper. “If you just looked at the national rates, you would be ignoring a big problem,” she says. “Such complexity in national and international patterns,” Pitman adds, means that “each country is forced to take a fine-grained approach to preventing [suicide].”

A similar urban-rural discrepancy occurred in India, according to a study lead by Prabhat Jha, a public health researcher at the University of Toronto, Canada. During 2010, the rate of suicide in rural areas was 20.4 per 100,000, nearly twice that seen in cities, a rate of 12.0 per 100,000. The paper suggests that the higher suicide rates seen in rural India than more urbanized parts of the country is in part due to greater access to pesticides, which are used in some suicide attempts. “Urgent research is needed to explore the reasons for suicide in young people and the large regional variations seen in this study,” the paper concludes.

The need for prevention may be particularly important given the dearth of psychiatric drugs and other treatments for suicide prevention, and the difficulty of arranging clinical drug trials for suicidal people, a topic explored in depth in a recent news feature in Nature Medicine.

Image courtesy of James Steidl via Shutterstock. 

Containment concerns persist at the proposed biosecurity lab in Kansas

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The US government continues to underestimate the potential of a dangerous pathogen escaping from a proposed BSL-4 containment biosecurity laboratory, according to an independent report published today.

A panel convened by the country’s National Research Council (NRC) concluded that an assessment completed earlier this year by the US Department of Homeland Security (DHS) overestimated the danger posed by tornadoes and earthquakes but underestimated the possibility of a disease being released by human error at the $1.14 billion National Bio- and Agro-Defense Facility (NBAF) in Manhattan, Kansas, which is slated to replace a half-century-old lab on Plum Island, New York.

“The DHS has just not established the safety of this facility,” Tom Manney, a retired Kansas State University geneticist and a member of No NBAF in Kansas, a group against the proposed facility, told Nature Medicine. “It may well be safe, but their analysis and how they’ve cherry-picked their data, and their assumptions give a very distorted and inaccurate view of it.”

Manney also thinks that Kansas politicians are selectively reading the NRC report. In a joint statement, US Senators Pat Roberts and Jerry Moran, both representing Kansas, together with the state’s governor, Sam Brownback, applauded the report’s authors for recognizing that the lab “would be a critical asset in securing the future health, wealth and security of the nation,” and they called on the DHS “to begin construction immediately.”

NIH working group changes tune, recommends more training grants

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Graduate students and post-docs in the biomedical field compete for limited research money from the US National Institutes of Health (NIH) and, after spending years in training, face uncertain career paths. A working group charged with studying these problems presented a report to NIH Director Francis Collins and his advisory committee yesterday—and offered some new solutions.

Back in March, the group said it was considering suggestions to reduce post-doc training grants and shifting the focus to programs that support work outside tenure-track academic research, where jobs are scarce. But it has shifted its tune about the means to achieving this goal. In their final report, they recommend increasing training grants, which require principal investigators to submit detailed research and mentoring plans as part of the application for funding. The NIH’s ‘R01’ research grants, however, make no such requirements.

At yesterday’s meeting, Shirley Tilghman, who co-chaired the working group and is also president of Princeton University in New Jersey, pointed to the current NIH budget crunch as forcing the rethink about its granting schemes. Ultimately, they hope that institutions will use more training and research grant money to support staff scientists, who are experienced researchers with graduate or doctoral degrees. “These trained scientists are sometimes treated like second-class citizens and they are the glue of our labs,” Tilghman told Collins and his advisors.

One way to shorten training time and free up individuals to kick-start their careers is for the NIH to cap funded projects at five years for institutions and six years for individuals, according to the report. It says that a faster track to the workplace would help the 45% of US-trained PhDs who pursue careers outside of academia. The committee also had ideas for helping graduate students get a head start on career development should they want to later leave the ivory tower. They recommended the creation of a program allowing academic institutions to apply for NIH money to develop programs that provide project management, business and entrepreneurial skills for graduate students only. The most successful programs could then be used as models at universities around the country. “What we’ve heard from industry is, ‘We get your graduates [from NIH] and we have to retrain them,’” says Tilghman.

But more than training, the best ideas come from a diverse group and a separate working group on diversity reported yesterday that the biomedical field still measured up short. With all other factors controlled for, African-Americans are still 10% less likely to be awarded NIH grants, said Reed Tuckson, co-chair of the working group and vice president of UnitedHealth Group headquartered in Minneapolis. Among other recommendations, the group suggested adding a chief diversity position to the NIH’s advisory committee to the director and encouraged Collins to use his “social capital” to encourage minorities to join the biomedical workforce. For his part, Collins promised both groups that today’s recommendations, unlike others in the past, would not be relegated to a shelf to collect dust. “A career in biomedicine is one of the most exciting things possible,” Collins told the group. “We want to make the field as attractive as possible for our young people.”

 

First vein grown from human stem cells successfully transplanted into a young girl

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First came bladders. Then pulmonary arteries. Followed by urethras, arteriovenous shunts and tracheas. Now, in another first for the world of tissue-engineered body parts, Swedish surgeons have successfully transplanted a bioengineered vein into a 10-year-old girl suffering from portal vein obstruction.

“This is a very good start for demonstrating what impact regenerative medicine can have on patients by using a biological matrix and seeding it with a patient’s own cells,” says Juliana Blum, cofounder and senior director of business operations at Humacyte, a North Carolina–based company developing bioengineered blood vessels for dialysis patients.

A team led by Suchitra Sumitran-Holgersson at the University of Gothenburg took a 9 centimeter-long snippet of vein from the groin of a deceased donor, stripped it of all cells and then reseeded the resulting hollow tube with stem cells taken from the recipient’s own bone marrow. Two weeks later, the surgeons transplanted the engineered conduit into the young girl. She remained healthy for close to a year, although a second procedure was then needed to lengthen the first graft after the vein started to constrict. Ever since the second transplant, in February of this year, the girl’s energy levels have improved and the blood flow to her kidneys are back to normal.

“The girl is somersaulting now,” says Sumitran-Holgersson, who reported the findings today in The Lancet. “Her parents told me, ‘We have a completely different child.’”

Ordinarily, when adults suffer the same problem as the girl who received the tissue-engineered blood vessel—a condition in which the vein that carries blood from the spleen and intestines to the liver is blocked—surgeons opt to transplant a patient’s own vein from the leg.  But this option is not feasible for young children because of the potential growth problems that can result from grafting in a still maturing body.

Christopher Breuer, a pediatric surgeon at the Yale University School of Medicine in New Haven, Connecticut, says the study represents an important next step for tissue-engineered technology. “This is a new application,” he notes. “This is the first time a bioengineered vein has been used in the portal circulation.”

As researchers try to make these procedures more routine, however, the use of stem cells on bioengineered grafts could face regulatory delays. “Whether real or not, regulatory agencies consider the risk of tumorogenesis or alterations in DNA a serious problem,” says Todd McAllister, cofounder and chief executive of Cytograft Tissue Engineering, a Novato, California company developing tissue-engineered blood vessels for people on dialysis for end-stage kidney disease.

Breuer, for one, is trying to overcome those obstacles. He is leading the first clinical trial in the US testing a tissue-engineered vascular product: a bioengineered blood vessel for children with a congenital heart defect. For more on his approach, see our 2011 news feature, ‘Taking tissue engineering to heart’.

Image courtesy of  Lightspring via Shutterstock

Microfluidic chips offer a SMART-er way to detect flu

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Tracking influenza outbreaks quickly and cheaply could get a whole lot easier thanks to a number of experimental devices that can accurately detect viral strains in an hour or so. Using microfluidic techniques, these ‘flu chips’ could lead to better disease surveillance and treatment

“We want to see better tests in the outpatient setting so physicians can get the best information available,” says CDC epidemiologist Dan Jernigan. “Within the last year we a have seen a number of these tests being developed.”

In March, Catherine Klapperich and her colleagues at Boston University described a miniaturized device embedded with tiny tubes that could extract flu RNA from a sample and amplify it using reverse-transcriptase polymerase chain reactions (RT-PCR) with 96% sensitivity. To her knowledge, no other assay previously used one chip for both tasks using a cohort of human samples.

In another first, Anubhav Tripathi and his colleagues at Brown University in Providence, Rhode Island, have developed a technique that relies on a DNA probe that binds and amplifies target viral RNA without relying on RT-PCR — a system the authors call a ‘Simple Method for Amplifying RNA Targets,’ or SMART. Reporting today in the Journal of Molecular Diagnostics, the researchers found that the SMART assay accurately detected flu in the lab, with studies involving clinical specimens underway to confirm the results. “They have done that through creative engineering of the primer and probes, and reengineering the assay development from the beginning,” says Klapperich, who was not involved in the Brown University study.

Importantly, unlike most laboratory-based assays currently approved for influenza testing by the US Centers for Disease Control and Prevention (CDC), these new point-of-care devices can be run under field conditions, thereby reducing the time from isolate sampling to diagnosis that can delay the pace of pandemic monitoring.

Beyond influenza, many groups are working on similar point-of-care diagnostics for a slew of other infectious diseases, too. Click below for a video about a new rapid and affordable way to detect HIV and syphilis in a developing world setting (as reported last year in Nature Medicine).

Image courtesy of anyaivanova via Shutterstock

Turning down the heat revs up brown fat

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This past winter, vests were a hot button issue thanks to then US presidential hopeful Rick Santorum. But a vest that cools—rather than warms—could fire up studies of brown fat as researchers seek drugs that turn on this calorie-burning tissue.

Compared with white fat, which mostly acts as an energy repository, brown fat serves to generate heat. In the past, researchers believed only babies made use of brown adipose tissue. Now we know adults have small deposits of brown fat throughout the body that burn energy only in chilly environments. With roughly two-thirds of the US classified as overweight, researchers are keen on pinpointing how brown fat is activated and how to convert white fat to its healthier cousin to help people slim down.

In February, Canadian researchers published a study in the Journal of Clinical Investigation that looked beyond brown fat’s heat-producing capabilities to how, once activated, it affects our metabolism. With a sample size of six healthy men, they reduced average skin temperature by about 4 degrees to roughly 30°C by fitting them in a cooling suit. Positron-emission tomography (PET) allowed scientists to see for the first time that cold exposure increased the amount of nonesterified fatty acids (NEFA)—the primary source of energy for tissues in fasting conditions—in the blood stream by one-third. Despite the small sample size, researchers expressed confidence in their results due to consistent measurements across the participants.

But it would be more convenient for overweight individuals to take a drug that causes brown fat to burn calories. A study published this week in the Proceedings of the National Academy of Sciences (PNAS) set out to test a possible drug therapy. Aaron Cypess of the Joslin Diabetes Center in Boston and his team wanted to determine if an ingredient found in over-the-counter decongestant drugs, called ephedrine, might activate brown fat without any cold exposure. A meta-analysis in 2003 had previously suggested that ephedrine may produce modest weight loss in humans. Ephedrine seems to cause weight loss by stimulating a release of the messenger molecule norepinephrine, thereby increasing heart rate. Brown adipose tissue has receptors for norepinephrine, so researchers reasoned the drug would activate this type of fat.

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Peptide shows potential to reverse skin fibrosis

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A counterintuitive discovery by a post-doc may open doors for eventual clinical trials testing the effectiveness of a synthetic peptide called ‘E4’ in fibrosis-related ailments. Individuals who suffer from fibrosis—a condition in which overproduction of the protein collagen leads to tissue thickening, scarring and, ultimately, organ damage—currently have no drug treatment options. Those lucky enough to get on an organ transplant list must impatiently wait.

“I think this study is intriguing,” says Paul Noble, a pulmonary specialist at Duke University’s School of Medicine in Durham, North Carolina. “The mechanism is unclear in terms of what E4 does to fibroblasts [cells found in connective tissue]. However, the study showed a dramatic clinical effect.”

{credit}Image courtesy of vetpathologist via Shutterstock{/credit}

E4 is a synthetic version of a peptide building block obtained from the natural protein endostatin, which prevents angiogenesis. In the past, studies have linked high endostatin levels in patients with ailments such as lung fibrosis. Yukie Yamaguchi, a post-doc at University of Pittsburgh’s School of Medicine in Pennsylvania, wanted to replicate in her lab how endostatin could possibly cause fibrosis. But the protein did not cause scarring as expected—instead it prevented the overproduction of collagen. Yamaguchi conveyed her findings to her mentor, Carol Feghali-Bostwick, who helped isolate a peptide portion of endostatin called E3. Since E3 easily degrades, researchers chemically modified it to create a more stable and effective peptide called E4.

The results, published online 30 May in Science Translational Medicine, show that E4, when injected under the skin of mice and in cultured human skin, can reduce fibrosis and even prevent it from forming. E4 appears to inhibit the transforming growth factor-β (TGF-β) responsible for ramping up the overproduction of collagen in human skin. It also reduced levels of an enzyme known as lysyl oxidase (LOX) that cross-links collagen and lowered levels of a transcription factor called early growth response gene-1 (Egr-1). The TGF-β–induced thickening of the cultured human skin samples and mouse skin decreased by 30% and 24%, respectively*.

Noble says continuing recent developments in fibrosis research have put the field at a tipping point for a drug therapy available on the market. But even if E4 goes into a clinical trial it would solve only a component of fibrosis. “There are three hallmarks of systemic sclerosis [a connective tissue disease]: immune system abnormalities, vascular changes and fibrosis. A peptide might benefit the fibrosis part of the disease but not other aspects of the disease,” says Feghali-Bostwick. However, she’s optimistic that her research could help a subset of patients: “Some diseases may be mostly fibrotic and the peptide may be more effective in those.”

Previous research has focused on the fibrotic aspects of connective tissue diseases. Massachusetts-based Biogen Idec, is currently recruiting patients for a phase 2 trial to test the efficacy of an antibody therapy called STX-100, says spokeswoman Amanda Galgay. STX-100 appears to interrupt the production of TGF-β. See our 2011 news feature, ‘Scarred by disease‘, to learn more.

*CORRECTION: An earlier version of this post inaccurately stated that cultured human skin samples and mouse skin decreased 75% in thickness after treatment.