Stories about: Science

A metabolic treatment for pancreatic cancer?

nitrogen disposal is important to pancreatic cancer
Targeting an enzyme that helps dispose of excess nitrogen curbed malignant growth of pancreatic tumors in obese mice.

Pancreatic cancer has become the third leading cause of cancer mortality. Its incidence is rising in parallel with the rise in obesity, and it’s hard to treat: five-year survival still hovers at just 8 to 9 percent. A new study published online in Nature Communications finds early success with a completely new, metabolic approach: reducing tumors’ ability to get rid of excess nitrogen.

The researchers, led by Nada Kalaany, PhD, of Boston Children’s Hospital’s Division of Endocrinology and the Broad Institute of MIT and Harvard, provide evidence that targeting the enzyme arginase 2 (ARG2) can curb pancreatic tumor growth, especially in people who are obese.

“We found that highly malignant pancreatic tumors are very dependent on the nitrogen metabolism pathway,” says Kalaany.

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Novel therapeutic cocktail could restore fine motor skills after spinal cord injury and stroke

CST axons sprout from intact to injured side
Therapeutic mixture induces sprouting of axons from healthy (L) into the injured (R) side of the spinal cord.

Neuron cells have long finger-like structures, called axons, that extend outward to conduct impulses and transmit information to other neurons and muscle fibers. After spinal cord injury or stroke, axons originating in the brain’s cortex and along the spinal cord become damaged, disrupting motor skills. Now, reported today in Neuron, a team of scientists at Boston Children’s Hospital has developed a method to promote axon regrowth after injury.

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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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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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From mice to humans: Genetic syndromes may be key to finding autism treatment

Boy and a mouse eye-to-eye
(Aliaksei Lasevich/stock.adobe.com)

A beautiful, happy little girl, Emma is the apple of her parents’ eyes and adored by her older sister. The only aspect of her day that is different from any other 6-month-old’s is the medicine she receives twice a day as part of a clinical trial for tuberous sclerosis complex (TSC).

Emma’s mother was just 20 weeks pregnant when she first heard the words “tuberous sclerosis,” a rare genetic condition that causes tumors to grow in various organs of the body. Prenatal imaging showed multiple benign tumors in Emma’s heart.

Emma displays no symptoms of her disease, except for random “spikes” on her electroencephalogram (EEG) picked up by her doctors at Boston Children’s Hospital. The medication she is receiving is part of the Preventing Epilepsy Using Vigabatrin in Infants with TSC (PREVeNT) trial. Her mother desperately hopes it is the active antiepileptic drug, vigabatrin, rather than placebo.

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Saving Vanessa part 2: Parent-driven science

DADA2 symptoms can be controlled with medications
Why did Vanessa’s mysterious rheumatologic condition cause her to have a stroke?

Two-year-old Vanessa had survived the unthinkable: two massive cerebral hemorrhages, nine days apart. Katherine Bell and her wife Nancy Mendoza felt immense relief at their daughter’s close call. But they wanted to know more. What had caused Vanessa’s strokes? Would there be more? Was the cause treatable?

The strokes were the culmination of a mysterious illness that had started with a rash. Because of high levels of inflammatory proteins in her blood, Vanessa’s rheumatologists, Pui Lee, MD PhD and Robert Sundel, MD, had given her a provisional, somewhat vague diagnosis of periodic fever syndrome.

“In rheumatology, we have to be comfortable with operating with a lot of unknowns,” Lee says.

But the strokes occurred despite three different anti-inflammatory treatments, which worked only temporarily. Bell, less comfortable with the unknowns, began searching the medical literature.

“It helped me feel calmer,” Bell says. “The more information I have, the less out of control I feel.”

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