Mitigating blood vessel damage from heart attack, stroke

Mouse hearts showing the impact of a therapeutic protein fusion on blood vessel health
Imaging of mouse hearts reveals widespread tissue damage (light-colored areas) after heart attack. At far right, however, mice that were treated with an engineered, optimized ApoM protein containing S1P have better tissue recovery than untreated mice (left) and mice that were given an inactive “dud” ApoM treatment (center). Credit: Hla lab/Boston Children’s Hospital

The average human has 60,000 miles of blood vessels coursing through their body. There are a number of mechanisms the body uses to keep that vast vascular network healthy, including a tiny fat molecule, a lipid called S1P, that plays a particularly important role.

S1P receptors dot the surface of the endothelium, a layer of cells that line the inside of all the body’s blood cells. Together, these so-called endothelial cells form a barrier between the body’s circulating blood and surrounding tissue. When S1P molecules activate their receptors, it suppresses endothelial inflammation and generally helps regulate cardiovascular health.

Now, researchers led by Timothy Hla, PhD, from the Boston Children’s Hospital Vascular Biology Program, report a novel therapeutic fusion that could trigger increased S1P receptor activity and recover blood vessel health following the onset of hypertension, atherosclerosis, stroke, heart attack and other cardiovascular diseases.

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If I knew then what I know now: The need for infrastructure to enable precision medicine

precision medicine - closing the infrastructure loop
For precision medicine to happen, we need to be able to close the loop when genetic discoveries are made.

Catherine Brownstein, MPH, PhD, is scientific director of The Manton Center for Orphan Disease Research at Boston Children’s Hospital. Kelsey Graber, MSc, is a research assistant in the Developmental Neuropsychiatry Program. Joseph Gonzalez-Heydrich, MD, is director of the Developmental Neuropsychiatry Program at Boston Children’s Hospital.

Research implicating rare genetic variants in medical and psychiatric diseases is quickly accumulating. This expanding knowledge should be taken into account when making treatment decisions for patients carrying these variants — as well as other family members — even when that knowledge comes after the patient is tested. But all too often, medical institutions are unable to go back and update the information given to families. We need a better infrastructure to enable precision medicine.

This problem recently surfaced in our psychiatry practice. It came to our attention because of a young boy with mild coordination delays and learning disabilities. At age 6, he started experiencing daily hallucinations such as voices telling him to kill his classmates.

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When asymptomatic viral infections turn deadly: Lessons from flies

Fruit flies

When Dr. Jonathan Kagan’s student came to him complaining of dying fruit flies, the two were unaware that their research was about to take an unexpected turn. Their goal in establishing Drosophila lines had been to study virus-host interactions. It was quickly subverted when the flies died on exposure to carbon dioxide, used when transferring flies between vials.

This was surprising on two fronts. First, carbon dioxide is routinely used to anesthetize the flies, with no ill effects. Second, the uninfected flies did not die. The virus used to infect the flies, called vesicular stomatitis virus (VSV), normally does not cause symptoms, even with the virus making several thousand copies of itself.

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Using ultrasound to trigger on-demand, site-specific pain relief

Ultrasound being applied to agitate injected liposomes, which then release nerve blocking medication that stops pain at the site
Ultrasound triggers the release of local anesthetics from injectable liposomes. Credit: Mary O’Reilly

According to the CDC, 91 people die from opioid overdoses every day in the U.S. Here in Massachusetts, the state has an opioid-related death rate that is more than twice the national average.

“Opioid abuse is a growing problem in healthcare,” says Daniel Kohane, MD, PhD, a senior associate in critical care medicine at Boston Children’s and professor of anesthesiology at Harvard Medical School.

Now, Kohane and other scientists who are developing triggerable drug delivery systems at Boston Children’s Hospital have found a new way to non-invasively relieve pain without opioids. Their novel system uses ultrasound to trigger the release of nerve-blocking agents — injected into specific sites of the body ahead of time — when and where pain relief is needed most. A paper describing the findings was published online today in Nature Biomedical Engineering.

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Nerve-growth agent could treat incontinence caused by spinal cord injury

Image of Rosalyn Adam, a urology researcher hoping to develop new treatments for incontinence, working in the laboratory
Rosalyn Adam is the director of urology research at Boston Children’s Hospital.

When the nerves between the brain and the spinal cord aren’t working properly, bladder control can suffer, resulting in a condition called neurogenic bladder. It’s a common complication of spinal cord injury; in fact, most people with spina bifida or spinal cord injury develop neurogenic bladders. Spontaneous activity of the smooth muscle in the wall of the bladder — called the detrusor muscle — commonly causes urine leakage and incontinence in people with neurogenic bladders.

“For children and adults, incontinence can be one of the most socially and psychologically detrimental complications of spinal cord injury,” says Rosalyn Adam, PhD, who is director of urology research at Boston Children’s Hospital. “The ultimate goal of our research is to return bladder control to the millions of Americans with neurogenic bladders.”

Now, Adam and a team of researchers think that they may have found a practical way to treat neurogenic detrusor overactivity by delivering medication directly into the bladder through self-catheterization, a practice that many people with neurogenic bladders already need to perform regularly.

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Botulism toxin X: Time to update the textbooks, thanks to genomic sequencing

botulinum toxin X
Botulinum toxin X is the first new botulinum toxin to be identified since 1969. (Jason Wilson/Flickr)

Botulism is a rare, potentially fatal paralyzing illness. It’s the reason we shouldn’t feed infants honey and why we need to take care in consuming home-canned foods: they can potentially contain nerve-damaging toxins produced by Clostridium botulinum. Botulinum toxin is classified as one of the six most dangerous potential bioterrorism agents.

There are seven known types of botulinum toxin. Toxins A and B were first identified in 1919, and first purified in 1946 and 1947, respectively. (Both are also used medically.) Toxins C, D, E and F eventually followed. The last, toxin G, was identified in 1969 in soil bacteria in Argentina.

And that’s where it’s stood until now. But to truly defend against botulism, we need to know all the toxins made by the various C. botulinum strains, since each requires a separate antibody to neutralize it.

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Another microbiome perspective: The host holds the leash

Abstract depiction of the microbiome

Most scientists and clinicians accept that the human microbiome impacts a person’s nutrition, immune system function, physical health and perhaps even mental illness, but exactly how or why is not well understood. Now, taking an evolutionary approach, a Boston Children’s Hospital infectious disease researcher suggests the host may play a more active role in controlling the microbiome than previously appreciated.

“I think we need to re-evaluate the way in which we think about the microbiome,” says Seth Rakoff-Nahoum, MD, PhD, a physician-scientist at Boston Children’s in the Divisions of Infectious Diseases and Gastroenterology, whose perspective was published today in Nature.

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Pediatric heart surgeons eye sticky, stretchy, slug-inspired adhesive

Arion subfiscus, whose sticky mucus inspired the new surgical adhesive (H. Crisp/Wikimedia Commons)

It’s been a challenge to develop a surgical adhesive that sticks to wet surfaces and isn’t toxic. But it turns out a certain kind of slug is very good at secreting a sticky mucus that glues fast, apparently as a defense mechanism.

That provided the inspiration for a hydrogel “super” adhesive that could supplant surgical sutures, at least for some operations, and help medical devices stay in place. Researchers at the Wyss Institute for Biologically Inspired Engineering and Harvard’s School of Engineering and Applied Sciences (SEAS), led by David Mooney, PhD, report that the adhesive bound strongly to a variety of animal tissues, including skin, cartilage, artery, liver and heart.

Nikolay Vasilyev, MD, a coauthor on the paper, is interested in the adhesive’s potential for young patients with congenital heart disease. He is is a research scientist in Cardiac Surgery at Boston Children’s Hospital, and led cardiac studies in pig models. 

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Building emotional strength with Mighteor: Will’s story

MIghteor

Will, a 13-year-old from Wisconsin, lives with high-functioning Asperger’s and faces difficulties recognizing and managing his emotions. He doesn’t like to talk about emotions he perceives as negative, and becomes upset when he doesn’t meet the high standards he sets for himself. These oachhallenges have made it difficult for Will to thrive in social situations.

Karen immediately began researching strategies, as many as she could find, to help Will manage his emotions. She found a Social Thinking program, as well as ABA therapy, both of them important opportunities for Will to increase his “social batting average,” as Karen puts it.

However, Will soon became resistant to using the strategies offered by these programs. Cues to calm down through deep breathing, for example, tended to create more frustration and anger and did not decrease his swearing, frustration or oppositional behaviors. Despite his ongoing work with an ABA therapist and the Social Thinking program, his academics started to suffer and he sometimes had to leave the classroom. “He would miss class, and then miss homework, and it would circle out of control,” says Karen.

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Robot-enhanced neurosurgery for nimbler seizure mapping

implanting electrodes for seizure monitoring, with robotic assistance
Scellig Stone and Joseph Madsen in surgery with the robot.

Head shaved, a little boy rests on the operating table, deep under anesthesia. His parents have brought him to Boston Children’s Hospital in hopes of determining the cause of his seizures. Now, neurosurgeons Scellig Stone, MD, PhD, Joseph Madsen, MD, and their colleagues in the Epilepsy Center are performing a procedure designed to monitor seizure activity in the 3-year-old’s brain.

But as the team members crowd around the table, they’re not alone. With the push of a button, a large robotic arm rotates and lowers right next to the boy’s head, helping the physicians pinpoint the precise location to drill. “This is a real game-changer,” murmurs one of the clinicians observing the surgery. “It’s going to transform the way we practice.”

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