Author: Nancy Fliesler

Protecting damaged hearts with microRNAs

microRNAs facilitate cardiac regeneration after a heart attack
New work advances the possibility of regenerating cardiac tissue after a heart attack. (PHOTO: ADOBE STOCK)

Once the heart is fully formed, the cells that make up heart muscle, known as cardiomyocytes, have very limited ability to reproduce themselves. After a heart attack, cardiomyocytes die off; unable to make new ones, the heart instead forms scar tissue. Over time, this can set people up for heart failure.

New work published last week in Nature Communications advances the possibility of reviving the heart’s regenerative capacities using microRNAs — small molecules that regulate gene function and are abundant in developing hearts.

In 2013, Da-Zhi Wang, PhD, a cardiology researcher at Boston Children’s Hospital and a professor of pediatrics of Harvard Medical School, identified a family of microRNAs called miR-17-92 that regulates proliferation of cardiomyocytes. In new work, his team shows two family members, miR-19a and miR-19b, to be particularly potent and potentially good candidates for treating heart attack.

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EEG patterns diverge in babies of stressed mothers

Study of newborn EEG and maternal stress
A study in JAMA Pediatrics assessed new mothers’ stress levels and EEG patterns in their 2-month-old babies. Such patterns could help flag infants at risk.(PHOTO: EMILY REILLY / BOSTON CHILDREN’S HOSPITAL)

Does exposure to stress early in life affect a baby’s brain development, and is there a way to single out babies who might benefit from early intervention? A two-center study led by Boston Children’s Hospital, published today in JAMA Pediatrics, used brain EEGs to begin to get at these questions in an objectively measurable way. It found that infants whose mothers reported high levels of stress have a distinct pattern of brain activity as measured by EEG — at only 2 months of age.

“The EEG has been found to be exquisitely sensitive to perturbations in the environment, and thus we are not entirely surprised to see an association between stress in a mother’s life and her infant’s brain activity,” says Charles Nelson, PhD, director of the Laboratories of Cognitive Neuroscience at Boston Children’s Hospital and the study’s senior investigator. “What we were surprised by, in part, was how early in life we see this association.”

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‘Nanobodies’ from alpacas could help bring CAR T-cell therapy to solid tumors

These alpacas produce the unusually small antibodies (nanobodies) used in a new form of CAR T-cell therapy
Like other alpacas, as well as camels and llamas, Bryson (left) and Sanchez produce unusually small antibodies that could have a role in cancer immunotherapy. (PHOTO COURTESY HIDDE PLOEGH / BOSTON CHILDREN’S HOSPITAL)

In 1989, two undergraduate students at the Free University of Brussels were asked to test frozen blood serum from camels, and stumbled on a previously unknown kind of antibody. It was a miniaturized version of a human antibody, made up only of two heavy protein chains, rather than two light and two heavy chains. As they eventually reported, the antibodies’ presence was confirmed not only in camels, but also in llamas and alpacas.

Fast forward 30 years. In the journal PNAS this week, researchers at Boston Children’s Hospital and MIT show that these mini-antibodies, shrunk further to create so-called nanobodies, may help solve a problem in the cancer field: making CAR T-cell therapies work in solid tumors.

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More efficient gene editing for blood stem cells could ease hemoglobin disorders

A new CRISPR strategy overcomes prior technical challenges. IMAGE: NANCY FLIESLER / ADOBE STOCK

The ability to edit genes in patients’ blood stem cells — which produce red blood cells, platelets, immune cells and more — offers the potential to cure many genetic blood disorders. If all goes well, the corrected cells engraft in the bone marrow and produce healthy, properly functioning blood cells… forever.

But scientists have had difficulty introducing edits into blood stem cells. The efficiency and specificity of the edits and their stability once the cells engraft in the bone marrow have been variable.

A new approach, described this week in Nature Medicine and in January in the journal Blood, overcomes prior technical challenges, improving the efficiency, targeting and durability of the edits. Researchers at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center and the University of Massachusetts Medical School successfully applied the technique to two common blood diseases — sickle cell disease and beta thalassemia — involving mutations in the gene for beta globin protein.

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Dually-targeted liposomes curb triple-negative breast cancer, metastases in mice

dual targeting for triple-negative breast cancer
(IMAGE: ADOBE STOCK)

Some 15 to 20 percent of all breast cancers are triple-negative, meaning they lack receptors for estrogen, progesterone and human epidermal growth factor type 2. They have the worst prognosis of all breast cancers and very limited treatment options. Finding a treatment that distinguishes between cancer cells and normal cells has been especially challenging.

A novel precision medicine strategy described today in Science Advances offers an intriguing ray of hope. Researchers at Boston Children’s Hospital, with bioengineers at the City College of New York (CCNY), showed that dually-targeted, antibody-guided nanoparticles, loaded with an existing chemotherapy drug, markedly improved tumor targeting, decreased tumor and metastatic growth and dramatically improved survival in a mouse model of triple-negative breast cancer. There were no observable side effects.

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The threat from mosquito-borne diseases: Forecasting mosquitoes’ global spread

Aedes albopictus
Aedes albopictus (ADOBE STOCK)

Outbreaks of mosquito-borne illnesses like yellow fever, dengue, Zika and chikungunya are rising around the world. Climate change has created conditions favorable to mosquitoes’ spread, but so have human travel and migration and accelerating urbanization, creating new mini-habitats for mosquitoes.

In Nature Microbiology yesterday, a large group of international collaborators combined these factors into prediction models that offer insight into the recent spread of two key disease-spreading mosquitoes — Aedes aegypti and Aedes albopictus. The models forecast that by 2050, 49 percent of the world’s population will live in places where these species are established if greenhouse gas emissions continue at current rates.

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How celastrol sensitizes brains to leptin, curbing hunger and obesity

celastrol path of action
Celastrol increases numbers of IL1R1 receptors in the brain, allowing leptin to act. (ILLUSTRATION: ELLA MARU STUDIO)

Here’s what’s known about celastrol, widely hailed in 2015 for its potent anti-obesity effects. It’s derived from the roots of the thunder god vine. It increases the brain’s sensitivity to leptin, the hormone that signals we’ve had enough to eat. It has curbed food intake by nearly 80 percent in obese mice, producing up to a 45 percent weight loss. It’s now in Phase 1 clinical trials conducted by ERX Pharmaceuticals; phase 2 studies are slated to begin this year.

What hasn’t been known is how celastrol makes the brain more sensitive to leptin. A study in today’s Nature Medicine finally provides an answer.

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50-year-old mystery solved — with clues to making more red blood cells

why steroids boost red blood cell production
Red blood cells produced by a single progenitor cell (IMAGE COURTESY HOJUN LI / DANA-FARBER/BOSTON CHILDREN’S VIA CELL PRESS)

Back in the 1950s, doctors began using steroids to treat Diamond-Blackfan anemia, or DBA, a severe condition in which patients cannot make enough red blood cells. There was no real rationale for using steroids, but there was no other good option, aside from regular transfusions. At the time, steroids were being thrown at seemingly everything.

But steroids worked in most patients, at least for a time — at the expense of serious side effects such as weight gain, bone loss, hypertension, diabetes and an increased risk of infections. A new study published yesterday in Developmental Cell finally explains why steroids work — and could provide a foothold for developing safer and better treatments for DBA. It could even pave the way to treatments for other types of bone marrow failure.

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EEG data classify ‘autism’ into two distinct groups

[IMAGES FROM BMC NEUROLOGY (DOI 10.1186/s12883-019-1254-1)]

The Diagnostic and Statistical Manual, 5th edition (DSM-5) established a single diagnosis of autism spectrum disorder (ASD) that includes Asperger’s syndrome, formerly considered a separate condition. The change was meant to eliminate diagnostic ambiguities, but it has encouraged schools to take a “one size fits all” approach, putting all children with autistic features in the same classroom.

This concerns many parents and professionals. “Typically, such classrooms focus on the more severely impaired, often non-verbally communicative children without helping the higher functioning children, such as those with Asperger’s,” says Heidelise Als, PhD, a psychologist at Boston Children’s Hospital.

Als and her co-investigator Frank Duffy, MD, a neurologist at Boston Children’s, decided to take an unbiased look at children diagnosed with autism, using data from their EEGs. In a paper in BMC Neurology, they conclude that autism is not a single entity, but falls into two distinct clusters — ripe for additional investigation.

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Eavesdropping on mitochondria, tissue by tissue

mitochondria
(IMAGE: ADOBE STOCK)

First in a two-part series on mitochondria. See part 2.

Mitochondria are essential to life: they produce energy, synthesize building blocks critical to cell function and help regulate cellular activity, including programmed cell death. Mitochondrial diseases can cause severe metabolic disorders in children and dysfunctional mitochondria are thought to play a role in cancer, diabetes, heart attack, stroke, Parkinson’s disease and more.

A new research tool offers an unprecedented glimpse at the workings of these tiny, dynamic organelles, and could aid in the study of mitochondrial dysfunction.

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