Prying into prion disease

Posted on 31 Jan 2011 by Elie Dolgin

A new diagnostic test could help doctors better identify prion diseases in living humans. Reporting online yesterday in Nature Medicine, researchers described a simple assay for detecting prions in cerebrospinal fluid taken from people suspected of suffering from Creutzfeldt-Jakob disease (CJD) that is more accurate and sensitive than existing tests that rely on post-mortem brain tissue.

“This technique allows definitive ante-mortem confirmation of CJD,” Ryuichiro Atarashi, a microbiologist at Nagasaki University in Japan who led the study, told Nature News.

The test involves using a shaking assay known as ‘real-time quaking-induced conversion’, which, if prions are present in the sample, causes other proteins to become misfolded. By adding a dye, researchers can then assess whether the number of abnormal proteins has increased.

In pilot studies involving 18 people with CJD, Atarashi and his colleagues showed that the prion disease was correctly diagnosed in 15 of the subjects. And in subsequent blind trials on 30 cerebrospinal fluid samples, the technique correctly pinpointed close to 90% of the CJD cases. The test also created no false positives in people confirmed not to suffer from the prion disease, the researchers found. By comparison, tests for levels of a CJD-specific protein known as 14-3-3 created far more incorrect diagnoses.

Steven Collins, director of the Australian National Creutzfeldt-Jakob Disease Registry and a co-author on the study, says that the new assay is “much more aligned to the actual disease” the previous diagnostics. “The hope is if we can more accurately and confidently say that the illness is CJD, then patients won’t be subjected to unnecessary invasive tests,” he told ABC.

Image of brain from CJD patient via Wikimedia

New mouse model paves the way for the development of hep C vaccines

Posted on 28 Jan 2011 by Michelle Pflumm

Researchers have created a new animal model for hepatitis C infection that could facilitate the development of new treatments for the disease.

Currently, the main therapeutic strategy for treating hepatitis C virus (HCV) infections involves the administration of a cytokine to modulate the immune system. However, this approach is difficult for patients to tolerate, often leading to excessive fatigue, nausea and anemia, among other ailments. New antiviral medications are on the horizon, but even these are not expected to help around 30% of people infected.

One critical roadblock to developing better treatment options is a lack of suitable mouse models. At present, researchers searching for new HCV therapies rely on chimpanzees, which are susceptible to HCV infection. This sensitivity could be because these primates also have cell surface proteins similar to those found in humans that are thought to facilitate viral infection.

Now, Charles Rice, a virologist at Rockefeller University in New York, and his colleagues have engineered mice susceptible to HCV infection by introducing two human protein receptors that facilitate virus entry into the liver. In a series of unpublished experiments presented on Monday at the New York Academy of Sciences, the Rockefeller team showed that vaccinated mice had lower rates of HCV infection compared to non-vaccinated controls. According to study lead author Alexander Ploss, another Rockefeller virologist, these mice can now be used to develop HCV vaccines and to search for new drugs to prevent re-infection in people who receive liver transplants as a result of HCV-triggered disease.

This study follows the introduction of another humanized mouse model — published online earlier this month from a team that included Rice and Ploss— that recapitulates liver disease characteristic of people suffering from chronic HCV infection.

For more on the quest to develop mouse models of HCV infection, check out our ‘community corner’ discussion on the topic.

Image: GrahamColm, Wikimedia

VIDEO: Going gaga at the bench

Posted on 27 Jan 2011 by Michelle Pflumm

Attention graduate students and postdocs. Ever wonder what to do with that research project that you’d been assigned that never seems to work according to plan? The students in Hui Zheng’s lab at Baylor College of Medicine in Houston have a solution. In the following video, they describe what to do when tasked with a bad project: they put on their best poker faces and then just dance.

NIH shores up plan to axe resource center and open new translational hub

Posted on 26 Jan 2011 by Michelle Pflumm

It’s official. Before the end of the year, the US National Institutes of Health (NIH) plans to dissolve its National Center for Research Resources (NCRR) and open a new center devoted to translational research.

Speaking at a NCRR advisory council meeting yesterday, Lawrence Tabak, deputy director of the NIH and co-director of the NCCR task force, presented a tentative framework for breaking up of the center, redistributing its programs and budgets, and reassigning all NCRR employees to comparable positions within the agency.

NIH officials first disclosed the plan to get rid of the NCRR last week on the institute’s blog Feedback NIH. Under the proposed arrangement, the new National Center for Advancing Translational Sciences (NCATS) — which was given the green light by the NIH’s Scientific Management Review Board (SMRB) last month — would take on the Clinical and Translational Science Awards program, while other branches of the agency, including the National Institute of General and Medical Sciences (NIGMS) and the National Institute on Minority Health and Health Disparities, would absorb other smaller programs. Meanwhile, an ‘interim infrastructure unit’ within the director’s office would oversee the bulk of NCRR’s portfolio until the most suitable agencies to administer them can be determined.

According to Tabak, a “smaller more focused” NCRR could be retained going forward. But last week, NIH director Francis Collins told ScienceInsider explicitly that NCRR was a goner.

Currently, the plan is to move ahead with NCRR’s dissolution by 1 October. However, many critics worry that this quick timeline for such a major agency restructuring does not allow for adequate input from the scientific community.

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Tuberculosis vaccine protects before and after infection

Posted on 24 Jan 2011 by Elie Dolgin

Researchers have developed a vaccine that can fight off tuberculosis infection both before and after exposure to the disease-causing bacterium. The vaccine, so far tested only in mice, was reported online yesterday in Nature Medicine.

“A vaccine which can both protect against initial infection and protect from a breakdown of infection into disease is a major breakthrough,” Peter Davies, secretary of the group TB Alert who was not involved in the research, told the BBC.

A team led by Peter Andersen from the Statens Serum Institut in Copenhagen, Denmark developed the experimental vaccine by combining two antigens expressed by Mycobacterium tuberculosis early during infection together with an antigen found only during persistent or latent infection. In experiments with mice, the researchers showed that the dual-action vaccine blocked the pathogen from taking hold after first exposure as well as prevented the bacteria from reactivating after lying dormant in the cell.

“The paper shows that it’s possible to target a vaccine also to antigens that are preferentially upregulated as bacteria adapt to long-term persistence and thereby change their antigenic compositions,” Andersen told Nature Medicine. “And by targeting these it is possible to prevent reactivation.”

Missed working group meeting on counterfeits is another fake out

Posted on 21 Jan 2011 by Michelle Pflumm

<img alt=“WHO.gif” src=“https://blogs.nature.com/nm/spoonful/WHO.gif” width=“160” height=“163” align=“right” hspace = “10px”/>The global war against counterfeit medicines took another step backwards this week.

The story begins last May, when the World Health Organization (WHO) said it would set up a working group to take a second look at the agency’s efforts to curb the number of fake drugs on the market. At the time, some people had criticized the WHO as being overly influenced by pharmaceutical manufacturers in its ongoing crusade against counterfeits. One particular sore point was the International Medical Products Anti-Counterfeiting Taskforce (IMPACT), which counts associations representing pharmaceutical manufacturers and wholesalers amongst its members.

But despite the WHO plan set forth last spring the working group on counterfeit, falsely-labeled and substandard medicines still has not met. Originally scheduled to meet in December, their report is expected at the upcoming meeting of the World Health Assembly in Geneva in May.

The health agency has had a rocky journey in its quest to address counterfeits. It has faced vocal criticism from India, a large manufacturer or generics, which struggled in the past with IMPACT’s broad definition of “counterfeit” drugs.

With the growing numbers of counterfeit and sub-standard medicines flooding the developing world, the move is especially disappointing. A WHO-study released last November indicates that as much as 70% of the anti-malarials and tuberculosis medications do not work against these growing epidemics. With these low-risk, high-reward crimes on the rise, something needs to be done, and done soon.

For more on counterfeits, read our news focus on the subject.

Canadian scientist who cemented stem cell theory dies

Posted on 21 Jan 2011 by Elie Dolgin

Ernest McCulloch, the Ontario Cancer Institute cell biologist who co-authored the first evidence demonstrating the existence of stem cells, died on Wednesday at the age of 84.

Together with his colleague James Till, McCulloch published a landmark paper in 1963 that defined the hallmark properties of stem cells — namely, the ability to self-renew and differentiate into other tissue. A lifelong scientist, McCulloch maintained an active research program studying the role of stem cells in acute myeloid leukemia, and even published a paper just last month on the radiation sensitivity of mouse bone marrow cells.

McCulloch was “a giant in Canadian health research,” Alain Beaudet, president of the Canadian Institutes of Health Research, told Nature Medicine in an email. McCulloch and Till’s “work provided the theoretical underpinning for bone marrow transplantation and advanced medical treatment of leukemia and autoimmune diseases. Their work also laid the foundation for the promising field of regenerative medicine.”

In 2005, McCulloch and Till took home the Lasker Award for Basic Medical Research — an accolade that prompted the two scientists to write this commentary in Nature Medicine reflecting back on their seminal research into the basic properties of stem cells.

FDA balks on medical device reform

Posted on 20 Jan 2011 by Michelle Pflumm

US Food and Drug Administration (FDA) regulators are calling for more guidance before implementing an internal working group’s recommendation to overhaul the approval process of medical devices.

The sweeping changes, recommended by the FDA’s Center for Devices and Radiological Health 510k working group last August, included mandates for additional clinical data for a new class of ‘medium-risk’ devices and post-approval surveillance of certain devices.

FDA officials yesterday announced that some of the recommendations would be implemented next March, including initiatives to streamline the approval of low-risk medical devices, but the agency plans to hold off on the most dramatic changes until an external panel convened by the US Institute of Medicine issues its recommendations, expected later this year.

The decision comes just days after Joshua Sharfstein, who led efforts at the FDA to toughen regulation of the medical device industry, stepped down as the agency’s deputy commissioner. In 2008, Sharfstein spearheaded an investigation into the FDA-approved knee replacement device Menaflex, manufactured by New Jersey-based ReGen Biologics, which ultimately resulted in the device being pulled off of medical supply store shelves.

The FDA announcement to hold off on major reforms is welcome news for medical device manufacturers, which are wary of further regulatory oversight and additional clinical work. Indeed, according to a PricewaterhouseCoopers report, medical device manufacturers are increasingly introducing their devices first overseas, presumably to dodge the FDA regulatory process.

Image by FitzColinGerald, Wikimedia

To combat Haitian cholera epidemic, researchers look to vaccines and early detection techniques

Posted on 19 Jan 2011 by Michelle Pflumm

More than a year after a catastrophic earthquake struck Port-au-Prince and killed an estimated 230,000 Haitians, public health officials are still grappling with the fallout from a cholera outbreak that has so far killed more than 3,000 people and infected nearly 150,000 others. To strengthen the response on the ground, the World Bank yesterday awarded $15 million to aid efforts in identifying and responding to future cases of the disease.

But global efforts are not stopping there. To prevent future cholera outbreaks, the World Health Organization is gearing up to implement a pilot cholera vaccination program to prevent the bacterial infection before it happens. However, as Nature reports, the effort is being hampered by vaccine supplies that are limited and that have never before been tested in disease outbreaks as large as the current epidemic.

With cases of cholera continuing to rise, methods are urgently needed to quickly identify contaminated water sources to prevent the spread of the disease. Reporting yesterday in the journal Bioconjugate Chemistry, a team from the University of Central Florida developed a method that could potentially do just that. The method, which uses the sugar dextran to detect the cholera toxin, the substance responsible for the disease, is comparable in sensitivity to existing methods but is much less expensive. What’s more, the authors report, the test could easily be adapted under field conditions such as those found in Haiti.

Death rates of cholera victims continue to drop to less than 1% in Port-au-Prince. But a news story out today from Nature cautions that many more people continue to be afflicted in rural areas of the country. Meanwhile, a team of scientists from the United Nations continues to search for the source of the cholera outbreak, Reuters reports.

Image of Vibrio cholerae from CDC

Compromise is in sight for new embryo research rules in France

Posted on 19 Jan 2011 by Elie Dolgin

By Barbara Casassus

PARIS — In 2004, France made a radical reversal by lifting its total ban on human embryonic stem cell research. But the law governing approval to conduct these types of studies remains convoluted, and scientists worry that the current system is dissuading companies from setting up research outfits in France. Proposals to update the French bioethics law will finally be presented to Parliament in early February, and a compromise may be on its way to help satisfy all partisans on this score.

Scientists are virtually unanimous in the opinion that the current ban with exemptions should be dropped, but politicians remain divided over the question. “The opposition comes mainly from the Roman Catholics and crosses party lines,” says Jean-Sébastien Vialatte, a parliamentarian and vice president of a special all-party National Assembly committee for the new law. Although France has been a staunchly secular country since 1905, “there has been strong pressure from the Church,” he adds.

The draft bill adopted by the cabinet of ministers last October still includes a ban on work involving human embryonic stem cells (hESCs) and embryos but has special exemptions for research that could lead to “major medical progress.” This is aimed to ease the current requirement in the 2004 French law that any approved research must have the prospect to bring “major therapeutic progress.”