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Nancy Fliesler

cancer genomicsIn 2012, Boston Children’s Hospital held the international CLARITY Challenge—an invitation to interpret genomic sequence data from three children with rare diseases and provide a meaningful, actionable report for clinicians and families. (Click for more background on the children, findings and winners.)

The full proceedings, published March 25 in Genome Biology, concluded that while the technical approaches were markedly similar from center to center, the costs, efficiency and scalability were not. Most variable, and most in need of future work, was the quality of the clinical reporting and patient consenting process. The exercise also underscored the need for medical expertise to bring meaning to the genomic data.

That was CLARITY 1. CLARITY 2, focusing on cancer genomics in children, promises to be exponentially more complex. Full story »

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MRI images showing isotropic diffusion in autism

A new MRI computational technology (above right) captures differences in water diffusion in the brain across a population of children with autism as compared with controls. This non-directional, “isotropic” diffusion pattern, not evident with conventional diffusion tensor imaging (DTI), may be an indicator of brain inflammation.

Diffusion tensor imaging (DTI), a form of magnetic resonance imaging, has become popular in neuroscience. By analyzing the direction of water diffusion in the brain, it can reveal the organization of bundles of nerve fibers, or axons, and how they connect—providing insight on conditions such as autism.

But conventional DTI has its limits. For example, when fibers cross, DTI can’t accurately analyze the signal: the different directions of water flow effectively cancel each other out. Given that an estimated 60 to 90 percent of voxels (cubic-millimeter sections of brain tissue) contain more than one fiber bundle, this isn’t a minor problem. In addition, conventional DTI can’t interpret water flow that lacks directionality, such as that within the brain’s abundant glial cells or the freely diffusing water that results from inflammation—so misses part of the story. Full story »

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metaphor for investors "shark tank"If you’ve ever watched Shark Tank, you’ve gotten a taste of venture capitalists’ (VC) innate skepticism and hard-nosed ability to triage ideas. A recent webinar hosted by Cambridge Healthtech Associates offered a good practical “101” for scientists, inventors and clinical innovators—which we’ve distilled into the six tips below.

1.  Find the pain.

VCs will want to know what “pain points” you are solving—the burning need or unpleasant thing a customer wants to avoid or fix right now. In health care, this could be the need for a more definitive diagnostic test or a cost-saving option, or, for the pharmaceutical industry, the need to reduce R&D costs by finding a better way to pick compounds to take to clinical trial. Full story »

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Hope for Rett syndrome?This post is the first in a two-part series on clinical trials in autism spectrum disorders. Read part 2.

In the world of neurodevelopmental disorders, an exciting trend is the emergence of specific molecular targets and treatments through genetic research. A case in point is IGF-1 therapy for Rett syndrome, a devastating disorder in girls that affects their ability to speak, walk, eat and breathe. It causes autism-like behaviors, intellectual disability and repetitive hand-wringing movements—a hallmark of the disorder.

A Phase I trial, published this week in the Proceedings of the National Academy of Sciences Early Edition, has modest but consistent results suggesting improvements in some salient features of the disorder.

Current treatments for Rett syndrome address only the symptoms and comorbidities, such as seizures, anxiety and scoliosis, but not the disease itself. But in 2007, findings in a mouse model (which even replicated the hand-wringing) changed how scientists think about Rett and other neurodevelopmental disorders, previously thought to be untreatable. Full story »

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A project that set out to build better shunts ended with potential ways to help kids avoid them altogether.

A project that set out to build better shunts ended with potential ways to help kids avoid shunts altogether.

Shunts often are surgically placed in the brains of infants with hydrocephalus to drain excess cerebrospinal fluid. Unfortunately, these devices eventually fail, and the problem is hard to detect until the child shows neurologic symptoms. CT and MRI scans may then be performed to check for a blockage of flow—followed by urgent neurosurgery if the shunt has failed.

Early detection of shunt failure was the problem pitched last fall at Hacking Pediatrics in Boston. Two bioengineers, Christopher Lee, a PhD student at Harvard-MIT Health Sciences and Technology program, and Babak Movassaghi, PhD, an MBA candidate at MIT Sloan, took the bait.

“We heard that parents would not take vacations in areas without an experienced neurosurgeon around,” says Movassaghi, a former Philips Healthcare engineer with 32 patents in cardiology and electrophysiology. “We were intrigued to solve that.” Full story »

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nanomedicineGood things, including therapeutics, can come in small packages—and increasingly this means nano-sized packages. For a sense of the scale of these diminutive tools, a strand of human DNA is 2.5 nanometers in diameter.

Nanomedicine offers the promise of drugs that are activated by physiologic stimuli in the body (like the shear stress of blood flow that’s partially blocked by a clot), that can home to very specific targets in the body (like pancreatic islets that are being attacked by the immune system in diabetes) and that carry their own imaging agents—a built-in “metric” to show that they’re working. Biomaterials are being crafted to enhance their properties—like adding gold “nanowires” to heart patches to increase their electrical conductivity.

Vector’s new sister publication, Innovation Insider, looks at the promise and challenges of nanomedicine—both technical and regulatory. Read more about nanoscissors, theranostics, quantum dots and how the future is nano.

If you’d like to receive Innovation Insider in your inbox, sign up here.

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Doctor handshake pediatric research partnershipOn the minds of everyone involved in the care of sick children is the pressing need for more pediatric research funding. Last November, Congress finally passed the National Pediatric Research Act. It authorizes the National Institutes of Health to support a nationwide network of up to 20 pediatric research consortia, but it falls short of actually increasing NIH spending. Indeed, the next step in implementing the Act is to secure a specific funding commitment from the NIH or Congress.

Currently, only about 5 percent of NIH’s budget goes to pediatric research. Rather than wait for the government, an editorial in Vector’s new sister publication, Innovation Insider, proposes that foundations and companies become active participants in the consortia.

The prospects for such alliances are good. Patient advocacy foundations are increasingly active in research, and academic-industry partnerships are on the rise. At Boston Children’s Hospital alone, sponsored research and collaborations with foundations and industry have tripled from nine in 2009 to 29 in 2013. Alan Crane, MBA, a partner at Polaris Partners and an advisor to Boston Children’s Technology and Innovation Development Office, points out that drug discovery is much harder and more complex today than it used to be—just as many products are coming off patent.

Read more on what makes these partnerships work.

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The Sylvian fissure (via BodyParts3D/Wikimedia Commons)

The Sylvian fissure (via BodyParts3D/Wikimedia Commons)

Five people with an unusual pattern of brain folds have afforded a glimpse into how the human brain may have evolved its language capabilities.

How the human brain develops its hills and valleys—expanding its surface area and computational capacity—has been difficult to study. Mice, the staple of scientific research, lack folds in their brains.

Christopher Walsh, MD, PhD, head of the Division of Genetics and Genomics at Boston Children’s Hospital, runs a brain development and genetics clinic and has spent 25 years studying people in whom the brain formation process goes awry. Some brains are too small (microcephaly). Some have folds, or gyri, that are too broad and thick (pachygyria). Some are smooth, lacking folds altogether (lissencephaly). And some have an abnormally large number of small, thin folds—known as polymicrogyria.

In 2005, studying people with polymicrogyria, Walsh and colleagues identified a mutation in a gene known as GPR56, a clue that this gene helps drive the formation of folds in the cortex of the human brain.

In a study published in today’s issue of Science, Walsh and his colleagues focused on five people whose brain MRIs showed polymicrogyria, but just in one location—near a large, deep furrow known as the Sylvian fissure, which includes the brain’s primary language area. Full story »

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Alison Frase with Nibs, a carrier of MTM whose descendants provided the basis for the gene therapy study.

Alison Frase with Nibs, a carrier of MTM whose descendants provided the basis for the gene therapy study.

Babies born with X-linked myotubular myopathy (MTM), which affects about one in 50,000 male births, are commonly referred to as “floppy.” They have very weak skeletal muscles, making it difficult to walk or breathe; survival requires intensive support, often including tube feeding and mechanical ventilation. Most children with MTM never reach adulthood.

One of these children, Joshua Frase, succumbed to MTM on Christmas Eve, 2010. The son of former NFL player Paul Frase, he lived to age 15. But his parents, who continue to actively support MTM research, now see a glimmer of hope for children born with the disease today.

A preclinical study on the cover of last week’s Science Translational Medicine, funded in part by the Joshua Frase Foundation, showed dramatic improvements in muscle strength using gene replacement therapy in mouse and dog models of MTM—paving the way for a potential clinical trial. Full story »

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Using a novel 3-D culture method, scientists were able to prod lung (bronchioalveolar) stem cells to produce colonies containing the cell type of choice: airway (bronchiolar) epithelial cells, alveolar epithelial cells or both. (Images: Joo-Hyeon Lee)

Using a novel 3-D culture method, scientists were able to prod lung (bronchioalveolar) stem cells to produce colonies with the cell type of choice: airway (bronchiolar) epithelial cells, alveolar epithelial cells or both. (Images: Joo-Hyeon Lee)

Someday it may be possible to treat lung diseases like emphysema, pulmonary fibrosis or asthma by prodding the lungs to produce healthy versions of the cells that are damaged.

That’s the hope of researchers Carla Kim, PhD, and Joo-Hyeon Lee, PhD, of the Stem Cell Research Program at Boston Children’s Hospital. In the Jan. 30 issue of Cell, they describe a pathway in the lungs, activated by injury, that directs stem cells to transform into specific kinds of cells—and that can be manipulated to enhance different kinds of repair, at least in a mouse model.

By boosting the pathway, Kim, Lee and colleagues successfully increased production of alveolar epithelial cells, which line the lung’s alveoli—the tiny sacs where gas exchange takes place, and that are irreversibly damaged in diseases like pulmonary fibrosis and emphysema. Full story »

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