Monthly Archives: July 2012

NIH emerges with new emergency medicine research hub

Posted on by
Reply

When a patient sits clutching his chest in pain in the emergency room, the doctor on call must think with razor-sharp focus to create a treatment plan immediately. The usual clinical suspects, such as heart attack or lung collapse, bear consideration. But anyone in emergency medicine research knows possible culprits vary widely and span the body’s organs. Unfortunately, research in this area has traditionally been spotty and uncoordinated — but perhaps not for much longer, thanks to the formation of a new Office of Emergency Care Research (OECR) unveiled earlier today by the US National Institutes of Health (NIH).

“You can hear the excitement in my voice,” says Jill Baren, an emergency medicine physician-scientist at the University of Pennsylvania Perelman School of Medicine in Philadelphia. “This new office will increase the scope and breadth of emergency medicine research and will allow an amazing amount of coordination.”

The new office will be housed within the NIH’s National Institute of General Medical Sciences with an annual budget of around $400,000, but it will not issue research grants. Instead, the OECR will serve as a clearinghouse for extramural, or off-campus, academic researchers engaged in emergency medicine projects. According to OECR acting director Walter Koroshetz, such coordination is necessary for a field like emergency medicine, which is a facet of almost all of the medical research agency’s institutes and centers. “Research in the emergency setting is on an exponential growth curve because it is such a laboratory for serious health conditions,” says Koroshetz, who also serves as deputy director of the National Institute of Neurological Disorders and Stroke.

For several years now, Baren and Koroshetz have worked together on an NIH-funded project that relies on emergency department data to study acute injuries and illnesses that affect the brain. Following the establishment of the OECR — which came about in part at the recommendation of the US Institute of Medicine, which issued a 2006 report highlighting the shortcomings of emergency medicine care in the country — this project and others will now be under the new office’s umbrella.

Image courtesy of SeanPavonePhoto via Shutterstock

Court ruling: FDA can regulate stem cell clinics

Posted on by
Reply

Cross posted from the Nature News blog on behalf of Monya Baker.

The FDA can block U.S. clinics that offer cultured cell products, according to a ruling of a U.S. district court this week.

Though championed by politicians like Governor of Texas Rick Perry, clinics marketing stem-cell procedures worry many healthcare advocates because these procedures are often heavily marketed but not thoroughly tested in clinical trials. (See Stem cell therapy takes off in Texas from nature.com and warnings compiled by the International Society for Stem Cell Research)

If cells are harvested and returned to a patient with “minimal manipulation”, the procedures are not regulated, but further processing classifies cell treatments as a drug, which requires FDA approval.

Read more on the Nature News blog.

FDA advisory panel looks positively on new eye drug

Posted on by
Reply

An independent advisory committee for the US Food and Drug Administration (FDA) today unanimously recommended the injectable drug ocriplasmin from the Belgium-based company ThromboGenics as an effective treatment for the age-related eye disorder known as symptomatic vitreomacular adhesion (VMA).

Currently, individuals diagnosed with VMA are offered either surgery or a ‘wait-and-see’ approach as their only options. “It’s always good to have a medication on the market [for eyes] that is injectable because if it works, then the patient avoids surgery,” Mayo Clinic retinal surgeon Sophie Bakri told Nature Medicine during a phone interview between scheduled surgeries in Rochester, Minnesota. Bakri was not involved in ThromboGenics’ clinical trials, but she has kept an eye on ocriplasmin’s progress.

VMA usually occurs in older adults—the average age in the clinical trials was 70 years—when the colorless jelly between the lens and the retina begins to shrink and forms an unusually strong adhesion to the retina. Over time, that pulling force can distort vision, causing straight lines to appear wavy, general blurriness and possibly a macular hole, resulting in complete loss of vision in the eye’s center. Ocriplasmin works by breaking apart the protein structure that attaches to the surface of the retina.

Maureen Kearny, a patient with VMA who participated in a phase 3 clinical trial site in Lawrenceville, New Jersey, told panel members during the public comment portion of the meeting that the next day after receiving her injection, “I was able to read the newspaper because the print was no longer distorted.” Kearny was one of the estimated 500,000 people in the US and EU combined who suffer from VMA, according to estimates from ThromboGenics.

But despite the mostly positive reception, advisory panel members did mention points of concern. One of those top worries was voiced by Wiley Chambers, director of transplant and ophthalmology products in the Center for Drug Evaluation and Research of the FDA in Rockville, Maryland. “After accounting for all patients whose vision decreased for reasons we understand, we still have a group of patients who experienced a 15-letter loss [in vision measurement] some time during the trial for which there is no immediate explanation,” Chambers said.

During phase 3 clinical trials for its drug, ThromboGenics also tested how a standard dose—125 micrograms administered only once—affects macular holes that can result from the disease. On this secondary study endpoint, the advisory committee expressed doubt. However, the panel decided no further studies would be necessary prior to the FDA’s final decision on the drug for the main indication of VMA, slated for 17 October.

While the FDA usually follows the advice of its advisory panels, it is not bound by those endorsements. Ocriplasmin, which may carry the trade name Jetrea, has also applied for approval in Europe. So the team at ThromboGenics is holding its breath on two continents for the moment.

Image courtesy of Alexonline via Shutterstock

Gene therapy to restore hearing sounds closer to reality after success in deaf-born mice

Posted on by
Reply

Using gene therapy, a team of researchers for the first time successfully restored normal hearing to mice born deaf due to a missing protein, according to a study published today in the journal Neuron. This finding could be music to the ears of people whose congenital hearing loss is caused by genetic mutations that may prevent tiny inner ear hairs from interacting with neurotransmitters that are necessary for hearing. In the current experiment, mice recovered full hearing for an average of seven weeks, with two of 19 mice maintaining it for as long as one and a half years. “I was completely shocked,” says lead author Lawrence Lustig, director of the Douglas Grant Cochlear Implant Center at the University of California, San Francisco. “The hearing looked almost completely normal and you couldn’t tell these were rescued mice.”

Richard Smith, a geneticist at Iowa State University in Iowa City who was not involved in the study, says that the findings offer hope for the estimated 12,000 infants, or 0.3 % of all babies born each year in the US, with severe-to-moderate hearing loss in one or both ears. “A hearing aid or cochlear implant doesn’t correct hearing in the same way that eyeglasses correct sight,” Smith explains. “Those devices only aid in hearing—hence the need for alternative treatments.”

Previous studies have introduced genes that cause deafness into mice and then applied gene therapy to remedy the problem, thereby using an artificial congenital hearing loss animal model. By comparison, the current study tested the approach using mice born without the Vglut3 mouse gene—which produces the protein known as vesicular glutamate transporter-3 (VGLUT3). Without this protein, the inner ear cells could not release the neurotransmitter glutamate, which carries sound signals to the brain. The researchers injected a harmless virus called adeno-associated virus type 1 (AAV1), which carried a working copy of Vglut3, into the ears of some animals one day after birth and in others almost two weeks post-delivery. They confirmed that both groups of treated mice could hear based on electrical signals picked up by electrodes attached to the scalp during an auditory brainstem response test. During that test, inner ear hairs send signals through the auditory pathway which goes through the brainstem. The control group of mice with this mutation received no injections and showed no response on hearing tests.

Lustig believes his study is a big step towards clinical trials—possibly in as soon as five years—to test gene therapy for congenital hearing loss in humans. But there’s one potential drawback to the study: the mouse gene Lustig used does not correlate with the same behavior of the mutant human gene SLC17A8. While a mutation in this gene in humans causes high-frequency hearing loss in adulthood, no studies have linked it yet to congenital deafness in people.

The researchers used the Vglut3 gene because they already had these knockout mice available in their lab. Smith says the choice was understandable and doesn’t take away from the significance of the study. “Gene therapy is complicated and very expensive and so you want to choose a model you have on hand already,” he adds.

Today’s study comes on the heels of a recommendation from a committee within the European Medical Agency to approve a gene therapy for people who lack an enzyme that breaks down fat in the body. Other companies, such as GenVec and Novartis, which are mentioned in earlier Nature Medicine coverage on hearing loss, continue to work on gene therapy that seeks to repair sensory hair cells in the inner ear.

Image courtesy of Phil Holmes via Shutterstock

 

Combination drug ‘sprinkles’ in the works for infants with HIV

Posted on by
1

WASHINGTON, DC — Last year, 330,000 infants were born infected with HIV, many of whom will succumb to the disease unless more baby-friendly formulations of antiretrovirals become available, AIDS advocates warned here yesterday at the International AIDS Society conference. “We know that existing treatments are very often difficult to administer,” Bernard Pécoul, executive director of the Drugs for Neglected Diseases initiative (DNDi), a Geneva-based non-profit that works to foster new treatments, told meeting attendees.

Newborns cannot swallow large pills, for example, and caregivers cannot crush tablets because this destroys their efficacy. Syrup-based formulations can be easier to administer, but bottles of these liquid drugs can be difficult to transport given their weight—a real issue in rural regions where this is done on foot—and families struggle with refrigerating and measuring the syrup, according to Adeodata Kekitiinwa-Rukyalekere, a pediatrician at Mulago National Hospital in Kampala, Uganda. What’s more, the suspension also contains alcohol, making the bitter taste of the medicine even more unpalatable than it already is.

In an effort to develop an effective and baby-proof option, last week DNDi announced a partnership with the Indian drug giant Cipla to develop the first four-in-one HIV drug combination in sprinkle form to address the unmet need of medicines for the very young. The sprinkles, which they aim to ultimately package in small, easy-to-transport packets, will contain the protease inhibitors lopinavir and ritonavir as well as the therapeutic agents abacavir and lamivudine.

In January, Gilead Sciences of Foster City, California, received approval from the US Food and Drug Administration for an oral powder version of the antiretroviral tenofivir (sold under the brand name Viread) for youngsters ages two to five. But “tenofivir is not indicated for very young children, and it’s just one drug” as opposed to a combination, says Jaideep Gogtay, head of the Medical Services division at Cipla, which is headquartered in Mumbai. Cipla already has a sprinkle version of lopinavir and ritonavir (which are sold together in high-income countries under the brand name Kaletra by Chicago’s Abbott Laboratories), and recent results from the CHAPAS-2 trial comparing these sprinkes against a syrup version revealed that 71% of families of children under the age of 1 in the trial chose to continue the sprinkles over the syrup after the study concluded.

The challenge now will be to create a granulized version that also contains abacavir and lamivudine (drugs currently marketed together by the UK’s GlaxoSmithKline as Epzicom or Kivexa) to enable the infants to receive all of the drugs in sprinkles, which could be given orally or mixed with food. Researchers in Cipla’s Mumbai labs will work to find a way to create granules that are coated to protect the drugs from the stomach’s acid environment, which can degrade the active ingredients.

If the creation of the four-in-one sprinkles goes according to plan, the partnership aims to begin clinical trials in 2015, according to Shing Chang, scientific advisor to DNDi.

MIT video models airports most likely to spread diseases

Posted on by
Reply

In a study released last week from the Massachusetts Institute of Technology (MIT), based in Cambridge, engineers show through computer modeling how major international US airports might contribute to the spread of contagious disease during the early days of an epidemic. The culprits that could contribute the most damage turn out to be airports in New York, Los Angeles and Honolulu, Hawaii. “Our work is the first to look at the spatial spreading of contagion processes at early times, and to propose a predictor for which ‘nodes’—in this case, airports—will lead to more aggressive spatial spreading,” said MIT computer engineer Ruben Juanes in a statement. The new model, unlike previous ones, considers the routines that passengers usually follow when traveling, an airport’s geographic location, how flights connect—or don’t—between airports, and, finally, how a long wait at an airport could influence how diseases spread.

Check out the video below.

 

One fish, two fish and 400,000 zebrafish

Posted on by
Reply

Hundreds of translucent creatures that biomedical researchers rely on for genetic insights settled into new digs today as researchers opened a newly refurbished and expanded animal repository called the European Zebrafish Resource Center. Housed at the Karlsruhe Institute of Technology (KIT) in southwest Germany, the center can maintain 400,000 live fish at maximum capacity in more than 3,000 tanks, and will include lab space for on-site zebrafish in vitro fertilization. Uwe Strähle, a geneticist at KIT, told Nature Medicine by phone after the ribbon-cutting ceremony that European zebrafish researchers eager to preserve their hard-won transgenic and mutant lines may begin submitting eggs to the center. Currently the center houses 300 transgenic lines but Strähle expected the collection to expand to hold thousands of lines in the next five years.

“Some mutant forms of zebrafish cannot be replicated so it is important to preserve those lines for future research,” Strähle explained. And as if capacity wasn’t enough, the center’s equipment might make any zebrafish investigator glassy-eyed with excitement. Located a few floors above the core aquarium room that will hold only frequently requested lines are brand-new PCR machines and freezers capable of storing 80,000 sperm samples in cryopreservation.

But Strähle thinks researchers will benefit most from the center’s screening lab, stocked with—among other neat toys—a single plane illumination microscopy machine that can be used to create 4-D images of the animals, including their traits. He envisions researchers visiting the screening lab to take advantage of the tools available to add or knock out genes and breed zebrafish lines needed for their future research.

In the past, European zebrafish researchers exchanged fish with US labs like the Zebrafish International Resource Center maintained by the University of Oregon, but the costs of sending little fish across the ocean kept going up. Zebrafish research in Europe can now make a big splash on its home turf.

Photo courtesy of Martin Lober, Karlsruhe Institute of Technology

 

Build a new biosafety lab, but possibly build it smaller, says report

Posted on by
Reply

Less than one month after a US National Resource Council (NRC) panel criticized the government for underestimating the risks of a proposed new biosecurity lab, a new ten-person committee issued a second report today advising that construction should go ahead, although possibly on a reduced scale from the original design.

The report comes at the request of the US Department of Homeland Security (DHS), which asked the NRC to weigh the pros and cons of three possible options: build the estimated $1.14 billion  National Bio- and Agro-Defense Facility (NBAF) in Manhattan, Kansas according to the original plans; build a scaled-back version of the facility with a distributed network of smaller affiliated laboratories; or continue using the half-century-old Plum Island Animal Disease Center in New York State.

The NRC committee was not tasked with choosing a best option, but it did come out with strong recommendations. For one thing, it basically nixed the possibility of keeping Plum Island open.

In a news conference this afternoon, committee chair Terry McElwain, director of Washington State University’s animal diagnostic lab in Pullman, described the ageing facility as “very outdated, inefficient,” and even with modifications, it “could not meet maximum level containment standards.”

Yet, even with the recommendation to begin construction on the Kansas facility, the report was mixed on what size and scope the lab should take. “The new lab as planned does meet the nation’s animal research needs, but it has a big drawback: the high cost,” McElwain said.

In this time of fiscal austerity, a scaled-back version of the facility could make a lot of sense, the report noted. And it would still be able to handle most research into emerging pathogens and diseases, although a planned vaccination research program would likely have to be dropped and possibly assigned to another high-level containment lab.

Still, stressed McElwain about the possibility of a smaller NBAF, “I want to make it clear this would not compromise the ability of cutting-edge research.”

Report image courtesy of the National Research Council

23andMe’s face in the crowdsourced health research industry gets bigger

Posted on by
Reply

The burgeoning field of do-it-yourself biomedical research got a major endorsement this week when the genetic testing heavyweight 23andMe announced it had bought the community health site CureTogether for an undisclosed sum.

With CureTogether, a social networking site that enables users to conduct their own research studies by sharing and aggregating health information, California-based 23andMe appears to be getting serious about expanding its efforts in the Web-based, participant-driven research arena.

Already, peer-reviewed studies involving 23andMe’s 150,000 customers have yielded novel genetic insights into Parkinson’s disease, hypothyroidism and common traits such as freckling. CureTogether’s infrastructure and user base—which span some 500 medical conditions—should only make such patient-driven research easier.

“There are tremendous opportunities for our members and for future research by integrating the 23andMe and the CureTogether platforms and phenotypic data,” CureTogether cofounder Daniel Reda, who will now serve as 23andMe’s senior product manager, said in a statement.

23andMe will face competition, though. PatientsLikeMe, Quantified Self and DIYgenomics are just a few of the community portals that now facilitate crowdsourced biomedical research. “Participatory health initiatives are becoming part of the public health ecosystem,” Melanie Swan, the founder of DIYgenomics, wrote in a study published earlier this year the Journal of Medical Internet Research.

Two years ago, Nature Medicine profiled one such participatory health startup called Genomera (see ‘Personalized investigation’ from our September 2010 issue). At the time, chief executive Greg Biggers was just developing the Palo Alto, California-based company’s platforms. But in the intervening years, Biggers has been busy tweaking the cloud-based software, testifying before the Presidential Commission for the Study of Bioethical Issues about amateurs participating in research and helping academics, as well as lay users, run analyses on his website.

Now, Biggers says his goal of a prospective, longitudinal study that can yield scientifically valid results has almost been achieved. Currently, the site hosts an ongoing study that is examining the effects of whole-fat butter on human cognition. (Biggers declined to share more details from the study on his beta site.)

“Since the first study we helped orchestrate [on vitamin B metabolism], we have proven two important items,” he says. “That participant-driven research is credible and productive, and that Internet study operations bring efficiency and scale to the world of health research.”

That’s a message that still has some skeptics in the ivory towers of most universities, but it doesn’t seem to have escaped 23andMe.

Photo courtesy of  Bruce Rolff via Shutterstock

Vaccine stabilization technique proves as smooth as silk

Posted on by
1

Vaccines and other biologic drugs quickly degenerate and lose their effectiveness if left out of the fridge for very long, creating a huge problem for healthcare delivery in less developed parts of the world. Fortunately, a new preservation technique could offer longer shelf lives. Reporting today in the Proceedings of the National Academy of Sciences (PNAS), researchers have discovered a silk protein capable of stabilizing heat-sensitive biologics for months at a time at room temperatures or even hotter.

“This work shows the high stability of silk and increases the chances of our ability to stabilize other drugs and bioactive molecules that are sensitive to heat,” says SU Kundu, who studies silk biomaterials at the Indian Institute of Technology in Kharapur and was not involved in the study.

A team led by David Kaplan, a chemical bioengineer at Tufts University in Medford, Massachusetts, purified the silk protein from silkworm cocoons and added the freeze-dried product to a commercial measles, mumps and rubella vaccine. They then exposed the silk-stabilized vaccine to the scorching temperatures common to many parts of the developing world — not to mention the US Northeast this past week — and showed the product retained the majority of its potency up to six months later. “This is the first study to successfully show how silk can be used in a commercially available vaccine,” he says.

According to Randy Lewis, a spider silk researcher at Utah State University in Logan, Utah, the secret to silk’s action as a vaccine preservative lies in its ability to encapsulate the attenuated viruses in the preparation and protect them from heat and moisture. “The silk is physically trapping the virus and preventing it from changing its structure,” he says.

Kaplan says the data are strong enough to merit testing of the silk-stabilized vaccine in the near future. “I would hope to see a clinical trial start within one year,” he says.

Image courtesy of Naypong via Shutterstock