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Tom Ulrich

Alprolix FDA approval recombinant factor IX rFIXFc hemophilia B coagulation

(Courtesy Biogen Idec)

A few weeks ago Vector brought you the backstory of how a clotting factor for hemophilia was made to last longer in the blood, allowing injections to be pared to once every week or two, rather than two to three per week.

Today we bring more good news: Following a successful Phase III trial, rFIXFc recently received the green light for marketing from the FDA and from Health Canada.

Developed by Biogen Idec under the trade name Alprolix™, rFIXFc—a modified version of clotting factor IX—is the fruition of a technology first envisioned by three researchers—gastroenterologists Wayne Lencer, MD, of Boston Children’s Hospital, and Richard Blumberg, MD, of Brigham and Women’s Hospital, and immunologist Neil Simister, DPhil, of Brandeis University—for large protein drugs. Their idea: to extend the drugs’ half-lives by protecting them from being ground up by cells. Full story »

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Stethoscope and keyboard health insurance claims dataThe only time most of us ever look at an insurance claim is after a hospital or doctor visit, when we get a claim summary from our carrier. And then as far as we know, it gets filed away, never again to see the light of day.

But there’s a lot to be learned from these claims data.

As with electronic medical records (EMRs), behind every claim an insurer receives is a detailed record about symptoms, tests, diagnosis and treatment. Properly compiled and analyzed, claims data can be an excellent resource for taking population-level snapshots of disease, helping to identify trends and reveal or probe associations.

That’s why claims data recently caught the eye of Kenneth Mandl, MD, MPH, and Mei-Sing Ong, PhD, two researchers in Boston Children’s Informatics Program (CHIP). Using claims records for roughly 2.5 million Americans, they turned their attention to two conditions—epilepsy and asthma—with interesting results. Full story »

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Ubiquitin RIG-I innate antiviral immunity Sun Hur

Ubiquitin (pink ovals) doesn't just tag proteins for recycling. It also may help keep our antiviral immune response in balance. (Image courtesy: Sun Hur)

If you follow cancer biology, then you’ve probably heard of ubiquitin before. Ubiquitin tags a cell’s damaged or used proteins and guides them to a cellular machine called the proteasome, which breaks them down and recycles their amino acids. Proteasome-blocking drugs like Velcade® that go after that recycling pathway in cancer cells have been very successful at treating two blood cancers—multiple myeloma and mantle cell lymphoma—and may hold promise for other cancers as well.

Less well known, however, is the fact that ubiquitin helps normal, healthy cells raise an alarm when viruses attack. Ubiquitin works with a protein called RIG-I, part of a complex signaling pathway that detects viral RNA and triggers an innate antiviral immune response.

Sun Hur, PhD, a structural biologist in Boston Children’s Hospital’s Program in Cellular and Molecular Medicine, has been studying RIG-I and other members of the innate cellular antiviral response for some time. And in a recent paper in Nature, she provided a structural rationale for how ubiquitin helps RIG-I do its job, and how that might help keep our immune system from getting out of hand.

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The platelet whisperers

by Tom Ulrich on March 27, 2014

Finding the switch that gets megakaryocytes to produce platelets

To manufacture platelets in the laboratory, we need to find the switch that starts their production.

Looking down at my bandaged finger—a souvenir of a kitchen accident a few nights prior—Joseph Italiano, PhD, smiles and says to me, “You should have come by, we could’ve given you some platelets for that.”

The problem is that Italiano really couldn’t; he needs every platelet his lab can put its hands on. A platelet biologist in Boston Children’s Hospital’s Vascular Biology Program, Italiano is trying to find ways to manufacture platelets at a clinically useful scale.

To do that, he needs to develop a deep understanding of the science of how the body produces platelets, something that no one has at the moment.

The path by which blood stem cells develop into megakaryocytes—the bone marrow cells that produce and release platelets into the bloodstream—is already known, Italiano says. We also know that platelets are essentially fragments of megakaryocytes that break off in response to some signal.

But that’s where our knowledge of platelet production largely ends. “Megakaryocytes themselves are something of a black box,” Italiano explains. “If you microinject the cytoplasm of an active megakaryocyte into a resting megakaryocyte, it will start to produce platelets as well. But we don’t know what factor or factors cause them to start platelet production.”

As Italiano and his laboratory peer into that black box, they know the stakes are big. Because in the end, they want to greatly reduce doctors’ and patients’ dependence on donated platelets. Full story »

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3D printed plastic model of a patient's skull John Meara craniofacial anomaliesA picture may be worth a thousand words, but there’s something about holding an object in your hands that’s worth so much more. I realized this when John Meara, MD, DMD, handed me the skull of one of his patients.

I turned it over in my hands while Meara, Boston Children’s Hospital’s plastic surgeon-in-chief, pointed out features like the cranium’s asymmetric shape and the face’s malformed left orbit.

Mind you, it wasn’t actually Meara’s patient’s skull in my hands. In reality, I was holding a high-resolution, plastic 3D model printed from the patient’s CT scans.

The printer that made that model—and several other models I saw in the last month—is the centerpiece of a new in-house 3D printing service being built by Peter Weinstock, MD, PhD, and Boston Children’s Simulator Program.

3D printing technology has exploded in the last few years, to the point where anyone can buy a 3D printer like the MakerBot for a couple of thousand dollars or order 3D printed products from services like Shapeways. Adobe even recently added 3D printing support to Photoshop.

And 3D printing is already making a mark on medicine. Full story »

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Meat grinder protecting protein drugs from being ground up by cells clotting factors

Cells can grind up large protein drugs. A new technology may help those drugs escape and stay in the bloodstream longer.

Getting drugs to stay in the bloodstream longer is a big deal when it comes to treating chronic diseases. You see, a drug’s half-life—the time it takes for half of a given dose to be cleared from the body—determines how long its effect(s) last.

If a drug’s half-life is short—meaning it’s cleared quickly—patients will have to take the drug frequently. Given that someone with a chronic condition could be on the medication for many years—say, patients with severe hemophilia, who endure frequent infusions of clotting factors—a short half-life can translate into high cost. Depending on side effects and how the drug is administered, quality of life may also suffer.

Several years ago, Wayne Lencer, MD, a researcher in Boston Children’s Hospital’s Division of Gastroenterology, Hepatology and Nutrition, and his collaborators Richard Blumberg, MD, at Brigham and Women’s Hospital (BWH) and Neil Simister, DPhil, at Brandeis University came up with a way to make protein-based drugs like clotting factors stay in the circulation longer: by keeping cells from grinding them up.

The first drug based on their work—a form of the factor IX clotting factor—just passed a Phase III clinical trial reported in The New England Journal of Medicine. Full story »

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Newborn baby neonatal sepsis developing world

Courtesy Anne Hansen, MD, MPH

Reducing child mortality is high on the list of the United Nations’ Millennium Development Goals—the eight global health, economic and development benchmarks set by the U.N. in 2000 for 2015.

While mortality among children under age 5 has improved greatly, the gains have largely been among children at the older end of that grouping. When it comes to mortality in the first week of life, little has changed.

“Early neonatal mortality rates haven’t decreased in the last two decades,” says Grace Chan, MD, PhD, a pediatrician at Boston Children’s Hospital, who conducts global health research at Harvard School of Public Health. “In developing countries, they still hover near 30 deaths per 1,000 live births.”

Early-onset infections—ones that arise within a week of birth—account for a significant portion of those deaths. Such infections may arise when a newborn picks up bacteria present in the mother’s birth canal during delivery, or from maternal infections during pregnancy.

In developed countries, interventions like prophylactic antibiotics and quick diagnoses help to keep neonatal infection rates low. But these kinds of interventions are less available in developing nations, where they could have the most impact. And while risk factors for neonatal infections have been well studied in developed nations, they are less  well known in resource-poor environments, where the infections most frequently occur.

To put it another way, when it comes neonatal sepsis in developing countries, there’s a lot we don’t know.

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Medicine on a keyboard - clinical trial data.Ed. note: This is the second in a two-part series on making clinical trial data more transparent. Click here for part 1.

To grossly oversimplify, there are two kinds of people in the world: those who want to see data from clinical trials made widely and freely available, and those who would rather have the data restricted for privacy or business reasons. And as we noted in our last post, there are valid arguments to be made on both sides.

But is there a way to balance the benefits of openness and the safety of confidentiality? Full story »

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clinical_trial_data_shutterstock_171501788Ed. note: This is the first in a two- part series on making clinical trial data more transparent. Click here for part 2.

2013 was the year when big data became, well, big. Everyone from investment companies to public utilities to security agencies—including medical researchers—are now clamoring for as much data on as many subjects and topics as they can get their digital hands on.

But while data in other fields are becoming ever more open, clinical trial data—especially from corporate-sponsored trials—are relatively hard for medical researchers to obtain. Full story »

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An empty restaurant table. Can measuring restaurant cancellations tell us something about flu outbreaks?You wake up feeling like someone has taken a jackhammer to your head. You’re feverish, aching all over and your stomach is doing somersaults. There’s no doubt about it: You have the flu.

You also have reservations for dinner tonight. So after a mug of tea and an ibuprofen, you grope for your phone and cancel the reservations you’d made through OpenTable.

That cancellation might be a signal to public health officials of a flu outbreak. Because, according to a study by HealthMap’s John Brownstein, PhD, and Elaine Nsoesie, PhD, reservation data from OpenTable could offer another view into the seasonal spread of the flu. Full story »

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