Author: Nancy Fliesler

Mapping mosaicism: Tracing subtle mutations in our brains

brain genetic mosaicism
(Erik Jacobsen, Threestory Studio. Used with permission.)
DNA sequences were once thought to be the same in every cell, but the story is now known to be more complicated than that. The brain is a case in point: Mutations can arise at different times in brain development and affect only a percentage of neurons, forming a mosaic pattern.

Now, thanks to new technology described last week in Neuron, these subtle “somatic” brain mutations can be mapped spatially across the brain and even have their ancestry traced.

Like my family, who lived in Eastern Europe, migrated to lower Manhattan and branched off to Boston, California and elsewhere, brain mutations can be followed from the original mutant cells as they divide and migrate to their various brain destinations, carrying their altered DNA with them.

“Some mutations may occur on one side of the brain and not the other,” says Christopher Walsh, MD, PhD, chief of Genetics and Genomics at Boston Children’s Hospital and co-senior author on the paper. “Some may be ‘clumped,’ affecting just one gyrus [fold] of the brain, disrupting just a little part of the cortex at a time.”

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3D printing helps doctors plan a toddler’s craniofacial surgery

Plastic surgeon John Meara, MD, and neurosurgeon Mark Proctor, MD, in the Craniofacial Anomalies Program at Boston Children’s Hospital are early adopters of 3D printing technology. They put it to good use in caring for Violet, a buoyant toddler who was diagnosed before birth with a rare, complicated skull and facial defect. Using CT images, and with the help of the hospital’s Simulator Program, they were able to build a series of plastic 3D models of Violet’s skull and rehearse her surgery—months before Violet arrived from Oregon.

“I actually feel like I know her, because I’ve seen that model change and grow over the last several months,” said Meara just before the surgery. “We can see and feel the trajectory of where we will have to make certain cuts, and that’s never been possible before.”

Read more on 3D printing in medicine in the Boston Globe. Follow Violet’s journey in this four-part series, and in The New York Times.

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Seizure-detecting wristband could prevent sudden death from epilepsy

“My biggest fear is that if I am not there to help him, when I wake him up he will be dead from seizures.”

That mother’s fear has a sound basis. The risk for sudden death from epilepsy, or SUDEP, is as high as 1 in 100 in the sickest children with epilepsy, says Tobias Loddenkemper, MD, of the Epilepsy Center at Boston Children’s Hospital. Many of those seizures occur in sleep.

Loddenkemper has been testing a novel wristband that uses motion and sweat sensors to detect the onset of a seizure—upon which the device would sound an alert. So far, the device has performed well on tests at Boston Children’s, picking up more than 90 percent of generalized tonic-clonic (grand mal) seizures, says Loddenkemper. But more work is needed to reduce false alarms (often generated when children are playing video games) and enable to device to spot more subtle seizures that are less convulsive in nature.

“This work is triggered by some very personal experiences of parents calling my office telling me their child died in sleep from seizures,” says Loddenkemper. “I dread these calls. We want to prevent those calls.”

The device manufacturer has created a fundraising site to help further the wristband’s development.

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Modeling pain in a dish: Nociceptors made from skin recreate pain physiology

Pain in a dish nociceptors

Chronic pain, affecting tens of millions of Americans alone, is debilitating and demoralizing. It has many causes, and in the worst cases, people become “hypersensitized”—their nervous systems fire off pain signals in response to very minor triggers.

There are no good medications to calm these signals, in part because the subjectivity of pain makes it difficult to study, and in part because there haven’t been good research models. Drugs have been tested in animal models and “off the shelf” cell lines, some of them engineered to carry target molecules (such as the ion channels that trigger pain signals). Drug candidates emerging from these studies initially looked promising but haven’t panned out in clinical testing.

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The 98%: Proteomics reveals proteins made from ‘noncoding’ DNA

proteins and peptides from noncoding DNA
Probing the genome's 'dark side' could change our view of biology.
Vast chunks of our DNA—fully 98 percent of our genome—are considered “non-coding,” meaning that they’re not thought to carry instructions to make proteins. Yet we already know that this “junk DNA” isn’t completely filler. For example, some sequences are known to code for bits of RNA that act as switches, turning genes on and off.

New research led by Judith Steen, PhD, and Gabriel Kreiman PhD, of Boston Children’s Hospital’s Proteomics Center and Neurobiology program, goes much further in mapping this “dark side” of the genome.

In a report published last month in Nature Communications, they describe a variety of proteins and peptides (smaller chains of amino acids) arising from presumed non-coding DNA sequences. Since they looked in just one type of cell—neurons—these molecules may only be the tip of a large, unexplored iceberg and could change our understanding of biology and disease.

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Seizure-detecting wristwatch moves forward: Embrace

As Epilepsy Awareness month closes out and we embark upon the holiday season, we’re pleased to see an innovation initiated here at Boston Children’s Hospital move toward commercial development. This wearable device for patients with epilepsy, called Embrace, is like a “smoke alarm” for unwitnessed seizures that may potentially prevent tragic cases of sudden, unexpected death from epilepsy (SUDEP) in the future.

The Bluetooth-enabled, sensor-loaded wristband, using technology developed and tested in collaboration with the MIT Media Lab, can detect the onset of a convulsive seizure based on the wearer’s movements and autonomic nervous system activity.

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‘Handoff’ tool cuts harmful medical errors 30 percent

Patient handoff I-PASSIt’s increasingly clear that good health care is as much about communication as about using the best medical or surgical techniques. That’s especially true during the “handoff”—the transfer of a patient’s care from provider to provider during hospital shift changes. It’s a time when information is more likely to fall through the cracks or get distorted.

Now there’s solid proof that focusing on communications counts. Last week, The New England Journal of Medicine (NEJM) published a paper showing that implementing a set of handoff procedures and training tools led to a 30 percent drop in injuries from medical errors across the nine participating sites.

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Rare disease: A difficult therapeutic path

Rare disease panelWhen a rare disease affects you or your family, it doesn’t seem rare. Add them all up, and rare diseases aren’t all that uncommon. What’s rare is for patients to receive effective treatments.

“There are 7,000 rare diseases, and under 400 approved drugs,” says Peter Saltonstall, president and CEO of the National Organization for Rare Disorders (NORD), “so there’s a huge opportunity there to try to develop more drugs.”

Saltonstall spoke today with five other panelists at Boston Children’s Hospital’s Global Pediatric Innovation Summit + Awards in a session titled, “Rare diseases: Lessons from the path less chosen.” David Meeker, MD, president and CEO of Genzyme, moderated.

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Gene discovery: When you’re the only patient with the disease

Gene Discovery Core rare diseaseVector took a moment this morning at the Boston Children’s Hospital Global Pediatric Innovation Summit + Awards to catch up with the Gene Discovery Core at the Manton Center for Orphan Disease Research. Its exhibition table doesn’t have fancy mannequins or flashy screens, but this team is rocking genetics and genomics, one patient at a time.

The usual methods for finding disease-causing genes don’t work for many patients who walk in the doors of Boston Children’s, or who mail in samples from all over the world. They may be one of just a handful of patients in the world with their condition—which may not even have a name yet.

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Hacking Pediatrics 2.0 in tweets

Hackers at Hacking PediatricsParents, clinicians, app developers, designers and more had 18 hours to prototype digital healthcare solutions at Hacking Pediatrics, produced by Boston Children’s Hospital and MIT Hacking Medicine. To accompany our earlier post, we created this Storify.

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