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Academic and industry partners are explicitly working to fill pharma pipelines.

Academic and industry partners are explicitly working to fill pharma pipelines.

Academic researchers and physician innovators are great at making research discoveries and developing inventions at an early stage. But if you were to fund them to turn their research findings into a product, would they have the expertise and experience needed to be successful? Most would not.

The investment community talks about the innovation funding gap, a.k.a. the “valley of death.” But there is also a knowledge gap on the part of academic researchers when it comes to transforming their technologies into therapeutics. Most want their findings to lead to new treatments for patients, but they lack the experience and expertise that companies have to advance early-stage research to a clinical stage. That includes expertise in designing pre-clinical experiments and navigating regulatory pathways for commercial development.

Academics often enter agreements with pharmaceutical companies, many of which are early-stage research grants. Often, these industry-sponsored research projects end with a scientific publication and are unsuccessful in generating new therapeutics—a subpar outcome for the company investor. Full story »

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dialysis nephrotic syndrome

Understanding the genetic causes of nephrotic syndrome could lead to better drug treatments that reduce the need for dialysis or a kidney transplant. (Image: Wikimedia Commons)

Nephrotic syndrome is one of the worst diseases a child can have. It strikes the filtering units of the kidney, structures known as glomeruli. There’s no good treatment: Steroids are the main therapy used, but 20 percent of cases are steroid-resistant. In the syndrome’s most severe form, focal segmental glomerulosclerosis (FSGS), children are forced onto chronic dialysis and often require a kidney transplant—often only to have their disease recur in the new organ.

Until recently, no one knew what caused nephrotic syndrome; the first causative gene was identified just a dozen years ago. The lab of Friedhelm Hildebrandt, MD, PhD, at Boston Children’s Hospital is one of a handful that’s been chipping away at the others.

Hildebrandt receives, on average, one blood sample a day from patients all over the world. Full story »

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My father had a favorite bit of advice as we embarked on our adult lives: “Go big or go home.” Going big is exactly what OPENPediatrics is doing, empowering physicians and nurses to care for children across the globe.

The Web-based digital learning platform was conceived 10 years ago by Jeffrey Burns, MD, MPH, chief of critical care at Boston Children’s Hospital, and Traci Wolbrink, MD, MPH, an associate in critical care. It concluded a year-long beta test in April 2014, and version 1 has now been launched.

Developed to impart critical care skills, OPENPediatrics uses lectures, simulators and protocols to deliver training. In the process, it has helped save lives. Full story »

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With initial help from her mother, Kailee West, 6, quickly masters the basics of Puddingstone Place, an interactive virtual environment that helps children with autism develop language skills.

With initial help from her mother, Kailee West, 6, quickly masters the basics of Puddingstone Place, an interactive virtual environment that helps children with autism develop language skills.

In the 1990s, Facilitated Communication (FC), in which assistants “facilitate” the typing of thoughts by minimally verbal children by supporting their hands, began raising hopes in the autism community. The unproven procedure caught fire, and Syracuse University established a nationally recognized Facilitated Communication Institute.

Upon closer examination, though, doubts emerged. The messages were surprisingly sophisticated and written by children who often were not even looking at the keyboard. Critics charged that the words were actually those of the facilitator rather than the patient. Studies and organizations began discrediting FC. Full story »

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brain malformations sequencing mosaicism

New methods can find mutations that strike just 1 in 10 cells in a sample.

It’s become clear that our DNA is far from identical from cell to cell and that disease-causing mutations can happen in some of our cells and not others, arising at some point after we’re conceived. These so-called somatic mutations—affecting just a percentage of cells—are subtle and easy to overlook, even with next-generation genomic sequencing. And they could be more important in neurologic and psychiatric disorders than we thought.

“There are two kinds of somatic mutations that get missed,” says Christopher Walsh, MD, PhD, chief of Genetics and Genomics at Boston Children’s Hospital. “One is mutations that are limited to specific tissues: If we do a blood test, but the mutation is only in the brain, we won’t find it. Other mutations may be in all tissues but in only a fraction of the cells—a mosaic pattern. These could be detectable through a blood test in the clinic but aren’t common enough to be easily detectable.”

That’s where deep sequencing comes in. Reporting last month in The New England Journal of Medicine, Walsh and postdoctoral fellow Saumya Jamuar, MD, used the technique in 158 patients with brain malformations of unknown genetic cause, some from Walsh’s clinic, who had symptoms such as seizures, intellectual disability and speech and language impairments. Full story »

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sensory processing autism

A mouse study explores how sound and touch information come together in the autistic brain (Image courtesy Nadine Gogolla)

Families of children with autism spectrum disorder have long noted sensory processing difficulties such as heightened sensitivity to noise, touch or smell—or even specific foods or clothing textures—earning sensory processing a place in the official DSM-5 description of the disorder.

“A high proportion of kids with autism spectrum disorder will have difficulty tolerating certain kinds of sensory inputs,” says Carolyn Bridgemohan, MD, co-director of the Autism Spectrum Center at Boston Children’s Hospital. Others, she adds, are less sensitive to certain stimuli, showing a higher tolerance for pain or excessively hot or cold temperatures.

A study published last week in Neuron uses mouse models to shed new light on the brain mechanisms that underlie sensory processing abnormalities in autism. Full story »

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peripheral nerve injury

Healing from nerve injuries gets slower as we age--here's why.

About six weeks ago, a glass shattered in my hand, severing the nerve in my pinky finger. The feeling in my fingertip still hasn’t returned, and now I know why: I’m too old.

Going back to World War II, it’s been speculated that recovery of peripheral nerve injuries—like those in limbs and extremities—is influenced by age. And studies indicate that peripheral neuropathy is common in people over 65, including those who have received cancer chemotherapy, and often unexplained.

“When you’re very young, the system is very plastic and able to regenerate,” Michio Painter told me recently. He is a graduate student in the laboratory of Clifford Woolf, PhD, director of the F.M. Kirby Neurobiology Center at Boston Children’s Hospital. “After that, there’s a gradual decline. By the age of 30, much of this plasticity is gone.”

Traditionally, this decline has been thought to reflect age-related differences in neurons’ ability to regrow, but when Painter studied neurons in a dish, he couldn’t confirm this. Full story »

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cell fate map Boston subway

Credit: Samantha Morris, PhD, Boston Children's Hospital

If you’ve lost your way on the Boston subway, you need only consult a map to find the best route to your destination. Now stem cell engineers have a similar map to guide the making of cells and tissues for disease modeling, drug testing and regenerative medicine. It’s a computer algorithm known as CellNet.

As in this map on the cover of Cell, a cell has many possible destinations or “fates,” and can arrive at them through three main stem cell engineering methods:

reprogramming (dialing a specialized cell, such as a skin cell, back to a stem-like state with full tissue-making potential)
differentiation (pushing a stem cell to become a particular cell type, such as a blood cell)
direct conversion (changing one kind of specialized cell to another kind)

Freely available on the Internet, CellNet provides clues to which methods of cellular engineering are most effective—and acts as a much-needed quality control tool. Full story »

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PTSD risk in adolescents after Boston Marathon bombingsDaniel Busso, MSc, is a doctoral student at the Harvard Graduate School of Education and a researcher in the Sheridan Laboratory at Boston Children’s Hospital.

More than 60 percent of teenagers have experienced a traumatic event in their lifetime, but only a minority will develop post-traumatic stress disorder (PTSD). For both researchers and clinicians, this raises an important question: Why are some youth at greater risk for mental health problems after trauma? As our lab reports in two recent studies, conducted after the 2013 Boston Marathon bombings, the answer may lie in our neurobiology.

PTSD, which includes intrusive memories, increased anxiety and difficulty concentrating or sleeping, has been linked to a variety of psychosocial and biological risk factors, such as prior experiences of trauma or a history of mental health problems. Other studies suggest that disruptions to the body’s stress response system, or in patterns of brain activity when responding to threat, may predispose people to the disorder.

However, a common problem in this research is that biological and mental health data are collected only once, usually long after the traumatic event itself, Full story »

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What's drawing lung cancer cells to migrate? (Juan Gaertner/Shutterstock)

What's drawing lung cancer cells to migrate? (Juan Gaertner/Shutterstock)

Ninety percent of lung cancer deaths are caused by the tumor’s spread—or metastasis—to other organs. Researchers have now discovered an approach to blocking metastasis in the most common type of lung cancer, adenocarcinoma, that potentially could be added to chemotherapy treatments aimed at shrinking the primary tumor.

Kerstin Sinkevicius, PhD, a research fellow at Boston Children’s Hospital, started with this question: Is there anything in a lung tumor’s environment that makes it metastasize? She sampled tissue from human lymph nodes—the first place cancers typically spread to—to see if the cells there were secreting anything that might lure cancer cells to migrate.

One chemical stood out: a growth factor called brain-derived neurotrophic factor, or BDNF. Secreted near maturing neurons, BDNF is best known for its role in stimulating the developing nervous system. Full story »

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