The Gutenberg press disseminated ideas to a wider society. But in the clinical world, much information is still on "lockdown." (Wikimedia Commons)
The best things in life are free: friends, sunny days, beautiful vistas. Wouldn’t it be nice if knowledge were also free? Historically, libraries promulgated knowledge sharing because it was for the public good. We see this spirit increasingly embraced on the Internet – take the recent announcement of a collaboration between Harvard and MIT to make their courses freely available to users around the world via the edX platform.
But have we made all useful knowledge available in a way that allows for the greatest societal advancement? Not really. According to Ken Mandl, MD, MPH, director of the Intelligent Health Laboratory at the Children’s Hospital Informatics Program (CHIP), one important source of information still on lockdown is clinical trial data. In an article called, “Learning from Hackers: Open-Source Clinical Trials” published this month in Science Translational Medicine (not currently available in full text), Mandl and his coauthors call for making raw, de-identified clinical trial data free to the public. Full story »
Surgeons and dentists often use Gelfoam sponges to mop up blood and help stop bleeding. Could they act as drug-eluting devices to grow new heart tissue?
While current heart-attack treatments mainly try to preserve healthy heart tissue, scientists have been finding ways to stimulate growth of new tissue to replace the tissue that’s damaged. They’ve done this either by getting heart muscle cells (cardiomyocytes) to make more copies of themselves, or by stimulating other cells to become cardiomyocytes (one recently reported study, for example, used genetic regulators called microRNAs).
The next challenge lies in getting these regenerative factors into a living patient’s damaged heart tissue — without affecting healthy tissue – and getting the factors to stay in place long enough to work their magic.
A new approach developed at Boston Children’s Hospital, which could be used relatively soon, takes advantage of Gelfoam, a gelatin-based sponge that’s already FDA-approved and has been used by surgeons and dentists for decades. Full story »
Small interfering RNAs, or siRNAs, could be great targeted treatment tools for breast and other cancers. The problem is making sure they get packaged and delivered to where they need to go. (pscf11/Flickr)
Breast cancers whose cells carry the HER2 protein are pretty tough customers. They only account for about 20 percent of all breast cancers, but they are some of the most aggressive. While targeted drugs like trastuzumab (Herceptin) and lapatinib (Tykerb) have made these tumors easier to treat, those that resist these drugs, relapse or don’t have HER2 on their cells’ surfaces can still stymie oncologists.
A molecular phenomenon called RNA interference (RNAi)—in which small pieces of RNA silence the expression of individual genes—could provide an alternative solution for breast and other cancers.
Though it was first discovered in plants, researchers have known for about a decade that small interfering RNAs (siRNAs) are active in mammals like us, and are already working on ways to harness them for shutting down genes promoting cancer and other diseases.
The problem with siRNAs for treatment, however, is making sure they get exactly where they need to go. That’s a problem that Judy Lieberman, MD, PhD, has taken a big step toward solving. Full story »
Early seizures may disrupt circuit formation in babies' brains, leading to autism. But new research suggests that an existing drug can reverse this.
This is the third post in a series about new approaches for seizures and epilepsy. Read the first and second posts.
We already know that there’s some kind of connection between epilepsy and autism: Children who have seizures as newborns not uncommonly develop autism, and studies indicate that about 40 percent of patients with autism also have epilepsy. New research at Boston Children’s Hospital finds a reason for the link, and suggests a way to break it — using an existing drug that’s already been given safely to children.
In the online journal PLoS ONE, Frances Jensen, MD, in the Department of Neurology and the F.M. Kirby Neurobiology Center at Boston Children’s, and lab members Delia Talos, PhD, Hongyu Sun, MD, PhD, and Xiangping Zhou, MD, PhD, showed in a rat model that early-life seizures not only lead to epilepsy later in life, but also produce autistic-like behaviors.
Drilling deeper, they showed that early seizures hyper-activate a group of signaling molecules collectively known as the mTOR pathway. Full story »
Brain MRIs from mice after stroke. Mice lacking Hv1 (right panels) had a much smaller volume of infarcted tissue than normal mice. Hv1 can also be blocked chemically.
Whether it’s in adults or in children with clotting disorders or other conditions such as sickle-cell disease, a stroke can be likened to an atomic bomb. Just as ongoing radiation can do more damage than the bomb itself, the secondary damage of a stroke can devastate the brain.
In an ischemic stroke, accounting for nearly 90 percent of all stroke cases, it happens like this: When vessels supplying blood and oxygen to the brain are blocked by a narrowing or a clot, immune cells in the brain sense the low-oxygen conditions, suspect an invading organism and try to kill it by producing molecules known as reactive oxygen species or ROS’s. These, unfortunately, have an inflammatory effect that actually damages the brain further, injuring and killing neurons.
“Stroke produces inflammation, and that’s one of the main things people have been after in trying to reduce stroke damage,” says David Clapham, MD, PhD, chief of the Basic Cardiovascular Research Laboratories at Boston Children’s Hospital.
Right now there’s nothing that can do this. Most existing stroke drugs are aimed at preventing the stroke or dissolving blood clots once the stroke is happening – but they can’t deal with the aftermath. Full story »
Leveling the immune system might let the body rebuild one that's tolerant of a transplanted kidney. (Photo: Tom Ulrich)
As the science of transplantation has gotten better, the patients whose lives are saved by other people’s organs are living longer and longer. But they’re paying a price—a lifetime of immunosuppressive drugs. William Harmon, chief of Nephrology at Children’s Hospital Boston, is trying to change that. Full story »
Manipulating the enzymes that turn genes on and off could help make the process of reprogramming cells into iPS cells a lot more efficient and safer.
There are several ways to reprogram skin cells into induced pluripotent stem (iPS) cells – cells that behave like embryonic stem cells, and which could help better understand the genetic basis of and develop new treatments for different diseases.
The major methods scientists use now include using viruses to deliver reprogramming genes or using RNAs to produce the necessary proteins without the genes. Different methods have different advantages and disadvantages, and some are more efficient than others.
What’s common across all of the methods is that they rely on four proteins to turn back the cellular clock – c-Myc, Klf4, Oct4, and Sox2. Less understood is whether enzymes that modify chromatin (the DNA-plus-protein package that constitutes our genome) play any role in the reprogramming process. These enzymes manage and control the cell’s epigenetic code – the layer of control that helps cells fine-tune gene expression by adding and removing small chemical tags to genes and proteins.
“During iPS reprogramming, a cell’s epigenetic code gets completely rewritten,” says George Q. Daley, director of the Stem Cell Transplantation Program at Children’s Hospital Boston. “But how the cell’s epigenetic enzymes influence the reprogramming process has been a mystery.” Full story »
In a four-way collaboration, skin cells from patients with autism will be used to make pluripotent stem cells. These will be made into neurons -- for study of what goes awry at the cellular level in autism, and for testing of drugs. (Miserlou/Wikimedia Commons)
In recent years, creative new partnerships have demonstrated big pharma’s recognition that academic medical centers hold many important cards in clinical research: scientific expertise, animal models of disease, patient samples and phenotypic data.
Increasingly, these partnerships involve academic and company researchers developing joint grant proposals in targeted areas, selected (by joint agreement) for company sponsorship. Some, like the Immune Disease Institute’s $25M arrangement with GlaxoSmithKline, are specific to one academic institution; others, like Pfizer’s Centers for Therapeutic Innovation (CTI) program, provide the same resources under the same deal structure to multiple institutions. Each new deal advances the interaction and understanding between academia and pharma around the common goal of finding new compounds and bringing them to clinic.
Now, in an exciting twist on its track record of partnerships with academic institutions, Roche has brought together three Harvard-affiliated organizations to screen and identify new drugs for the treatment of autism spectrum disorders (ASDs). Full story »
Valentine's Day is Innovation Day (image: Richard Giles/Flickr)
In a series of 17 short TED-style talks next Tuesday, February 14, clinicians and scientists from Children’s will present new products, processes and technologies to make health care safer, better and less expensive. The event, from 1-5 p.m. Eastern, is sponsored by the Innovation Acceleration Program. It’s now running a wait list, but you can also watch the live stream or track the proceedings on Twitter (#iDay) or via @science4care. Here’s a small sampling of next week’s presenters; for details, read the press release or view the full agenda.
Diagnosing lazy eye when it’s most treatable: in preschoolers
If lazy eye, or amblyopia, is caught early – ideally, before age 5 – it’s easily treated by patching the “good” eye, forcing the child to use and strengthen the weaker eye. But if it goes unnoticed, the weak, unused eye can slowly go blind, Full story »
Spherical nanoparticle (Fangting/Wikimedia Commons)
Recent research on Type 1 diabetes has begun focusing on prevention: Studies indicate that children start developing diabetes-related autoantibodies sometimes years before they develop clinical diabetes requiring insulin shots. The autoantibodies are an indicator of insulitis – a precursor condition in which the insulin-producing islets in the pancreas become inflamed and infiltrated with white blood cells.
In animal models, immune-suppressing drugs have been shown to blunt this attack by curbing the number of white blood cells circulating in the body. That reduces the need for insulin treatment – but at a high cost: Given systemically, the high doses needed to suppress the immune attack cause kidney toxicity, reduce the ability to fight infections, and decrease the body’s ability to respond to insulin.
That’s a tough sell for a child who doesn’t yet have symptoms of diabetes – but that’s where nanotechnology can help, say researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University and Children’s Hospital Boston. What if immunosuppressants could be delivered in far smaller doses, just to where they’re needed in the pancreas? Full story »
