Author: Nancy Fliesler

The autism-GI link: Inflammatory bowel disease found more prevalent in ASD patients

brain gut connection autism IBD ASDReports from parents and a growing number of studies over the past 10 to 15 years suggest that children with autism spectrum disorder (ASD), especially more severe ASD, are prone to gastrointestinal disorders. Researchers have attributed the association to altered GI microbiota, abnormal intestinal physiology, immune alterations and other mechanisms. Some speculate that the connection results from unusual eating patterns in children with ASD.

A 2012 study led by bioinformatician Isaac Kohane, MD, PhD, of Boston Children’s Hospital and Harvard Medical School grouped autism patients according to the gene expression patterns in their blood, and one group had altered immunologic and inflammatory pathways. A more recent study went a step further, finding similar gene expression profiles in the intestines of children with ASD and those with inflammatory bowel disease (IBD).

Looking at IBD (Crohn’s and colitis) sets the bar a little higher, since IBD is uncommon and also unlikely to be caused by dietary factors (though it can certainly be aggravated by them). In a new study in the journal Inflammatory Bowel Disease, Kohane and colleagues crunched three large databases to create what they believe is the largest ASD/IBD study to date.

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Hold me, turn me: 3D printed models help doctors rehearse tricky cerebrovascular procedures

Vein of Galen-3D-20140418_Orbach-croppedFour children with life-threatening malformations of blood vessels in the brain appear to be the first to benefit from 3D printing of their anatomy before undergoing high-risk corrective procedures.

The children, ranging from 2 months to 16 years old, all posed particular treatment challenges: cerebrovascular disease often entails complex tangles of vessels in sensitive brain areas.

“These children had unique anatomy with deep vessels that were very tricky to operate on,” says Boston Children’s neurosurgeon Edward Smith, MD, senior author of the paper and co-director of the hospital’s Cerebrovascular Surgery and Interventions Center. “The 3D-printed models allowed us to rehearse the cases beforehand and reduce operative risk as much as we could. You can physically hold the 3D models, view them from different angles, practice the operation with real instruments and get tactile feedback.”

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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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