Author: Nancy Fliesler

Supercharged marrow transplant: Zebrafish reveal drugs that aid engraftment

Zebrafish stem cell engraftment bone marrow
(Jonathan Henninger and Vera Binder)

Bone marrow transplantation, a.k.a. stem cell transplantation, can offer a cure for certain cancers, blood disorders, immune deficiencies and even metabolic disorders. But it’s a highly toxic procedure, especially when a closely matched marrow donor can’t be found. Using stem cells from umbilical cord blood banked after childbirth could open up many more matching possibilities, making transplantation safer.

Except for one problem. “Ninety percent of cord blood units can’t be used because they’re too small,” says Leonard Zon, MD, who directs the Stem Cell Research Program at Boston Children’s.

But what if the blood stem cells in those units could be supercharged to engraft more efficiently in the bone marrow and grow their numbers faster? That’s been the quest of the Zon lab for the past seven years, in partnership with a see-through zebrafish called Casper.

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MRI-powered ‘millirobots’ could swim around the body, drive needles, puncture tissues

(noppasit TH/Shutterstock)
(noppasit TH/Shutterstock)

MRI is a staple of surgical imaging, but it has the potential to do much more than take pictures. In 2011, bioengineer Pierre Dupont, PhD, and colleagues demonstrated that an MRI machine’s magnetic field could power a motor strong enough to control a robotic instrument, in this case driving a needle into an organ to do a biopsy.

But Dupont, head of the Pediatric Cardiac Bioengineering Lab at Boston Children’s Hospital, wants to go further. “We had this idea, admittedly fanciful: What if you could swim robots through the body?” he says. “If you could inject something systemically and steer it to just hit your target, that would be a cool application.”

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Does autism stress families’ chromosomes?

telomeres autismThe ends of our chromosomes have little caps called telomeres that keep our DNA from degrading as our cells divide. Telomere length is partly determined by genetics. However, telomeres also shorten as we age and as a result of health conditions, including stress—as in institutionalized children in Romania and women caring for children with chronic illnesses.

An intriguing new study in the July Journal of the American Academy of Child and Adolescent Psychiatry finds shortened telomeres not just in children with autism (confirming a recent study from China) but also in their infant siblings and their mothers. An effect was also seen in fathers, but it didn’t reach statistical significance.

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Gene therapy restores hearing in deaf mice

A closeup of the sensory hair bundles in the cochlea (inverted v's), each containing 50 to 100 microvilli tipped with TMC proteins. Cell bodies are below the bundles. (Gwenaelle S. Geleoc & Artur A. Indzhykulian)
The inverted V’s above are sensory hair bundles in the ear, each containing 50 to 100 microvilli tipped with TMC proteins. Gene therapy restores hearing by providing working copies of those proteins. (Gwenaelle Geleoc & Artur Indzhykulian)

More than 70 different genes are known to cause deafness when mutated. Jeffrey Holt, PhD, envisions a day when patients with hearing loss have their genome sequenced and their hearing restored by gene therapy. A proof-of-principle study published today by the journal Science Translational Medicine takes a clear step in that direction, restoring hearing in deaf mice.

“Our gene therapy protocol is not yet ready for clinical trials—we need to tweak it a bit more—but in the not-too-distant future we think it could be developed for therapeutic use in humans,” says Holt, a scientist in the F.M. Kirby Neurobiology Center at Boston Children’s Hospital and an associate professor of Otolaryngology at Harvard Medical School.

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Power to the people: Citizen science meets precision medicine for rare disease

At this recent GoldLab Symposium presentation in Colorado, parent Matt Might shows how it’s done.

People credit rapid next-generation gene sequencing for the increased pace of medical discovery. But patients and their families—especially those with rare or undiagnosed conditions—are emerging as the true engines of precision medicine. Racing against the clock to save their children, parents are building databanks, connecting scientific dots and fueling therapeutic advances that could otherwise take a decade or more to happen.

“There’s a culture shift,” said Isaac Kohane, MD, PhD, chair of Harvard Medical School’s Department of Biomedical Informatics (DBMI), which hosted a conference titled Precision Medicine 2015: Patient Driven in late June. “A culture shift where patients feel empowered morally and intellectually to lead in precision medicine research and delivery.”

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Breaking the allergic asthma cycle…by targeting nerve endings

asthma therapeuticsExisting asthma medications work by suppressing inflammatory signaling by immune cells or by dilating constricted airways. Over time, though, these drugs’ benefits can wane. New research supports a surprising new tactic for controlling asthma: targeting sensory nerve endings in the lungs with a selective drug.

Our lungs are known to contain specialized sensory neurons known as nociceptors that connect to the brainstem. Best known for causing the perception of pain, nocieptors also trigger the cough reflex in the lungs when they detect potential harms like dust particles, chemical irritants or allergens. Nociceptor nerve endings are known to be more plentiful and more readily activated in people with asthma. Now it’s also clear that they help drive allergic inflammation.

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Gene therapy to germline editing: Promises, challenges, ethics

A report this April rocked the scientific world: scientists in China reported editing the genomes of human embryos using CRISPR/Cas9 technology. It was a limited success: of 86 embryos injected with CRISPR/Cas9, only 71 survived and only 4 had their target gene successfully edited. The edits didn’t take in every cell, creating a mosaic pattern, and worse, unwanted DNA mutations were introduced.

“Their study should give pause to any practitioner who thinks the technology is ready for testing to eradicate disease genes during [in vitro fertilization],” George Q. Daley, MD, PhD, director of the Stem Cell Transplantation Program at Boston Children’s Hospital, told The New York Times. “This is an unsafe procedure and should not be practiced at this time, and perhaps never.”

As Daley detailed last week in his excellent presentation at Harvard Medical School’s Talks@12 series, the report reignited an ethical debate around tampering with life that’s hummed around genetic and stem cell research for decades. What the Chinese report adds is the theoretical capability of not just changing your genetic makeup, but changing the DNA you pass on to your children.

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Gene for salivary enzyme found unrelated to obesity

(Jaimie Duplass:Shutterstock)
child eating cracker-cropped-shutterstock_169956-Jaimie Duplass

Sometimes it’s just as important to rule a gene out as the cause of a condition as it is to rule it in, especially for complex, multi-gene traits like obesity. In a report published yesterday by Nature Genetics, a gene once thought to be the single greatest genetic influence on human obesity actually has nothing to do with body weight.

The study, led by researchers at Harvard Medical School (HMS) and Boston Children’s Hospital, also provides the first effective ways to analyze complicated parts of the genome.

The gene in question, AMY1, encodes an enzyme in our saliva that helps convert starch into sugar. “There’s been some speculation that because this enzyme helps get nutrients out of our food, it could be linked to obesity,” said Christina Usher, a graduate student at HMS and first author on the paper.

What’s complicated is that people can have anywhere from 2 to 14 copies of AMY1—or more. In 2014, an unrelated international group reported in Nature Genetics that people with fewer than four copies of AMY1 had a roughly eight times greater risk for obesity than people with more than nine copies of the gene. AMY1 therefore appeared to be protective.

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Treating chronic pain: From humans to mice and back

"Reverse engineering" reveals the enzyme sepiapterin reductase (SPR)—the large gray molecule in the background—as a new target for pain treatment. This take on Michelangelo's famous Sistine Chapel image symbolizes the link between human pain patients and the mouse model. The lab-designed SPR inhibitor (in green), shown within SPR’s active pocket, is the "bridge" between the two species. (Image: Alban Latremoliere)
“Reverse engineering” reveals the enzyme sepiapterin reductase (SPR)—the large gray molecule in the background—as a new target for pain treatment. This take on Michelangelo’s famous Sistine Chapel image symbolizes the link between human pain patients and the mouse model. The lab-designed SPR inhibitor in green, shown within SPR’s active pocket, is the “bridge” between the two species. (Image: Alban Latremoliere)

Non-narcotic treatments for chronic pain that work well in people, not just mice, are sorely needed. Drawing from human pain genetics, an international team demonstrates a way to break the cycle of pain hypersensitivity without the development of addiction, tolerance or side effects. Their findings were published online today in the journal Neuron.

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Early adversity and the brain: Bangladeshi children may provide lessons

neuroimaging adversity Bangladesh
Children from the neighborhood around the neuroimaging lab

Dhaka, Bangladesh, is a megacity, one of the world’s fastest growing. By 2025, the U.N. predicts, Dhaka will be home to more than 20 million people as rural migrants swell its population. Many residents live in extreme poverty, crowded into dense, hot, chaotic slums with open sewers and corrugated housing.

While traditional global health programs have focused on curbing infectious disease, low-resource settings like Dhaka are also coming to be seen as “living laboratories” for investigating how adversity affects children’s brain development. Last year, the Bill & Melinda Gates Foundation awarded a two-year, $2.5 million grant to Charles Nelson, PhD, to bring the first fully equipped neuroimaging facility to Bangladesh.

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