Stories about: biomarkers

Fast brain waves: A better biomarker for epilepsy

EEG and MEG detection of HFOs, fast brain waves associated with epilepsy
Localization of fast brain waves, called HFOs, with scalp EEG (left) and MEG (right). HFOs present a new biomarker for areas of the brain responsible for epileptic seizures.

In the U.S., about one in 100 people have some form of epilepsy. A third of those people have seizures that cannot be controlled with drugs, eventually requiring surgery to remove the area of their brain tissue that is triggering seizure activity.

“If you can identify and surgically remove the entire epileptogenic zone, you will have a patient who is seizure-free,” says Christos Papadelis, PhD, who leads the Boston Children’s Brain Dynamics Laboratory in the Division of Newborn Medicine and is an assistant professor in pediatrics at Harvard Medical School.

Even experts in this field were skeptical for years about the non-invasive detection of HFOs. But now, thanks to our study and other researchers’ work, these people are changing their minds. At present, however, these surgeries are not always successful. Current diagnostics lack the ability to determine precisely which parts of an individual’s brain are inducing his or her seizures, called the epileptogenic zone. In addition, robust biomarkers for the epileptogenic zone have been poorly established.

But now, a team at Boston Children’s Hospital is doing research to improve pre-surgical pinpointing of the brain’s epileptogenic zone. They are using a newly-established biomarker for epilepsy — fast brain waves called high-frequency oscillations (HFOs) — that can be detected non-invasively using scalp electroencephalography (EEG) and magnetoencephalography (MEG).

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Search for brain tumor biomarkers in urine strikes gold

Urine Vascular Biology Program netrin brain tumor biomarker Edward Smith Michael Klagsbrun

A good biomarker is one whose levels go up or down as a patient’s disease worsens or wanes. A great biomarker also gives key insights into disease development. A really great biomarker does both of these things and also serves as a treatment target.

With a protein called netrin-1, Edward Smith, MD, and Michael Klagsbrun, PhD, seem to have hit the trifecta. In a recent paper in Cancer Research, they report a clear relationship between urine netrin levels and medulloblastoma, the most common malignant brain tumor of children.

And show that netrin fuels the tumor’s invasion into healthy brain tissue.

And that blocking netrin may, at least in the laboratory, check the tumor’s spread.

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Anticipating autism through functional neuroimaging

Mila-cap-ball-2014-05-08 12.24.14Is 9-month-old Mila Goshgarian at risk for developing autism spectrum disorder (ASD)? Her 4-year-old twin brothers are both on the spectrum, so statistically her chances are at least 20 percent.

Her mother, Tonia, brought her into Boston Children’s Hospital for the Infant Sibling Project, which works with babies who are at increased risk of developing ASD in hopes of discovering early brain biomarkers for the disorder. This is Mila’s fifth visit; she’s been coming to the Labs of Cognitive Neuroscience for testing since the age of 3 months.

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Finding the best stem cell for the job

Although stem cells have the potential to differentiate into any type, they often prefer a particular route (Flickr/Jonathan Billinger)
Although stem cells have the potential to differentiate into any type, they often prefer a particular route. Could scientists take advantage of that? (Flickr/Jonathan Billinger)
Some people are born football players, others are made for basketball: Yi Zhang, PhD, reaches often for this metaphor as he explains his research with stem cell differentiation, recently published in Stem Cell Reports.

Stem cells are well-known for their ability to differentiate, or transform, into different types of cells. Two types of stem cells—embryonic stem cells and induced pluripotent stem cells—are able to ultimately change into any human cell. But that doesn’t mean all stem cells in these groups are equal: They have certain molecular features that bias them toward transforming into particular cell types. The ability to predict a stem cell’s differentiation bias would enable scientists to select a specific embryonic or induced pluripotent cell line to create cells for different applications—like grooming some youth athletes for football, others for basketball.

Zhang’s lab has identified a gene that acts as a powerful biomarker—physical or chemical characteristic whose appearance heralds a particular process—predicting a pluripotent stem cell’s tendency to differentiate into endoderm, cells on the inner layer of an embryo that become lung, digestive tract, pancreas and liver cells. It could be the first of a family of genetic biomarkers that guide scientists trying to create different cells and tissues for regenerative medicine.

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A day in the life: A pediatric neurosurgeon’s vision

Ed Smith explains the moyamoya operation during a live webcast.

Lindsay Hoshaw contributed to this post.

It’s 7 a.m. and neurosurgeon
Ed Smith, MD
, is downing a Diet Coke as he reviews the MRIs of today’s patients. He sprints up a stairwell to greet his first patient in the pre-operating wing.

Thirteen-year-old Maribel Ramos, about to have brain surgery at Boston Children’s Hospital, sits in her bed fidgeting. Smith reassures her about the operation, promises they’ll shave off as little hair as possible, and gets Maribel to crack a smile by telling her he moonlights as a hairdresser.

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Catching—and avoiding—long-term rejection of heart transplants

As the close of American Heart Month draws near, let's take a moment to learn what two teams of scientists are doing to help heart transplant patients keep their new hearts in the long run. (englishsnow/Flickr)

You’re a heart transplant patient. You’ve been on the waiting list for months, maybe years. Now, you’re being wheeled out of the operating room, a donated heart beating in your chest.

You’ve finished one journey, but are only just starting on a new one: keeping your body from rejecting your new heart.

Luckily for you, new methods under development could help tell early on when chronic rejection problems—the kind that arise five or 10 years after your transplant—start to loom. And even better, scientists are homing in on a new way to prevent chronic (and maybe short-term) rejection from happening in the first place.

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Biomarkers for all

Just about any measurable molecule that changes with health and disease could be a biomarker. (David Guo's Master/Flickr)

Your doctor has a lot of tools to detect, diagnose and monitor disease: x-rays, MRIs, angiography, blood tests, biopsies…the list goes on.

What would be great would be the ability to test for disease in a way where there’s no or low pain (not invasive) and lots of gain (actionable data about the disease process itself, its progression and the success of treatment).

That’s where biomarkers come in.

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Breast cancer and estrogen: Blocking ADAM to save Eve

Breast cancers that start off vulnerable to hormone-based treatments often lose that vulnerability over time. A protein called ADAM12 is being developed into a diagnostic and prognostic biomarker, and might also hold the key to treating women with such tumors. (Illustration: Durer’s “Adam and Eve")

About two-thirds of breast cancers are fueled by estrogen, making them quite vulnerable to drugs like tamoxifen that interfere with the hormone. But some 50 percent of such hormone-sensitive tumors start shrugging off tamoxifen treatment at some point and continue to grow.

Marsha Moses and her team in Children’s Vascular Biology Program want to turn the tide against these estrogen- or hormone-independent tumors, which are much more difficult to treat. And they think a protein named Adam – or rather, ADAM12 – might hold the key.

The story starts seven years ago with a search for cancer biomarkers in a fluid far removed from the breast: urine. Over the years, Moses, the program’s director, has collected a large biorepository of human urine and other samples, as well as associated clinical data, which she and her lab use to search for proteins whose presence is associated with different cancers.

In 2004, Moses and her postdoctoral fellow Roopali Roy discovered that the amount of ADAM12 rises in the urine of women with breast cancer as their cancer progresses.

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Vector’s upcoming coverage of BioPharm 2011

Vector and Children’s Hospital Boston’s Technology and Innovation Development Office (TIDO) at will be enthusiastic participants in next week’s BioPharm America conference (Sept 7-9).  In between networking with industry colleagues and pitching technologies developed at Children’s, we’ll be providing blog coverage and live-tweeting from the sessions under the hashtag #BPA11.

Since BioPharm is in Boston this year, we’re also heavily involved as presenters. Bruce Zetter of Children’s Vascular Biology program will speak about cancer biomarkers on a Wednesday panel titled Lessons Learned in Personalized Medicine in Oncology. Leonard Zon, director of Children’s Stem Cell Program, will describe the development of stem-cell-boosting drugs as part of a Friday panel titled Stem Cells and Drug Discovery: Confronting the Translational Imperative.

And Erik Halvorsen, director of Children’s TIDO, is a panelist in Wednesday’s session titled: Pharma’s Interest in Collaborating Early: Flavor of the Month or Viable Business Model?

Halvorsen elaborates on this theme in an interview for the online life sciences journal Partnering News.

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Early brain checkups for dyslexia, autism and more

Researchers are seeking to track the brain at earlier and earlier ages (here, the brain of a newborn baby born 10 weeks prematurely). © FNNDSC 2011

For the third year running, my daughter is participating in a dyslexia study she entered at age 5, just after finishing preschool. Thinking she was part of a game, she spent about 45 minutes lying still in a rocket ship (in reality, an MRI scanner), doing mental tasks she believed would help lost aliens find their way back to their planet.

All the while, her brain was being imaged, helping a team led by Nadine Gaab of Children’s Laboratories of Cognitive Neuroscience to find a pattern indicating that she might be at risk for dyslexia. Such signatures might flag children who could benefit from early intervention, sparing them the frustration of struggling with dyslexia once in school.

Getting brain MRIs from young childrenwithout resorting to sedation — is a difficult feat (Gaab and colleagues shared their protocol in the Journal of Visualized Experiments). But as reported in today’s Boston Globe, Gaab and Children’s neuroradiologist Ellen Grant are pushing the envelope even further, trying to find MRI signatures of dyslexia in infants.

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