Author: Nancy Fliesler

Human brain evolution holds clues about autism… and vice versa

human brain evolution autism Human Accelerated Regions
Humans evolved to become more social and cognitively advanced, thanks to genetic changes in regions such as HARs — the child with autism spectrum disorder (ASD) being the exception. While mutations in protein-coding genes continue to be explored in ASD (indicated by the red ribbon of RNA), the scientists at far left are suggesting that mutations in regulatory elements (the histones , in green, and their modifications shown in yellow) may be important in both ASD and human evolution. (Illustration: Kenneth Xavier Probst)

Starting in 2006, comparative genomic studies have identified small regions of the human genome known as Human Accelerated Regions, or HARs, that diverged relatively rapidly from those of chimpanzees — our closest living relatives — during human evolution.

Our genomes contain about 2,700 HAR sequences. And as reported today in Cell, these sequences are often active in the brain and contain a variety of mutations implicated in autism and other neurodevelopmental disorders.

Read Full Story | Leave a Comment

I feel good! How mood influences time management

time management and mood
(JESHOOTS/Pixabay)

Most theorists boil human behavior down to a pursuit of pleasure. Yet all of us engage in mundane, even unpleasant activities. It’s called being an adult, right? Happy Monday!

But Maxime Taquet, PhD at the Computational Radiology Laboratory at Boston Children’s Hospital (who by day helps conduct advanced brain imaging in children with neurologic conditions) wondered why. If we’re such pleasure-seekers, how do we muster the will to do our taxes or vacuum the house?

Taquet, with Jordi Quoidbach, PhD, of the Department of Economics and Business at the University Pompeu Fabra in Barcelona, and other colleagues developed a smartphone app to track the activities and moods of more than 28,000 French-speaking people for an average of 27 days. At random times during the day, the app asked users to rate their current mood on a scale of 0 to 100 and indicate what they were doing at that moment from a list of options.

Read Full Story | Leave a Comment

Topical antibiotics for otitis media: A one-squirt cure?

otitis media transtympanic gel
A single-application gel could revolutionize treatment of ear infections, reducing side effects and drug resistance. (Click to play animation.) Credit:Kohane group

Otitis media, or middle-ear infection, affects 95 percent of children and is the number one reason for antibiotic prescriptions in pediatrics. Typically, antibiotic treatment involves 7 to 10 days of oral medication — several times a day — a formidable task for parents of little kids.

“Force-feeding antibiotics to a toddler by mouth is like a full-contact martial art,” says Daniel Kohane, MD, PhD, a pediatrician and director of the Laboratory for Biomaterials and Drug Delivery at Boston Children’s Hospital.

A single-application bioengineered gel could be the answer to parents’ and pediatricians’ prayers. Described in a paper published today in Science Translational Medicine, the gel would provide an entire course of therapy through a single squirt into the ear canal. It was developed by Kohane’s team in collaboration with investigators at Boston Medical Center and Massachusetts Eye and Ear.

Read Full Story | Leave a Comment

Keeping up with HIV mutations: Building a nimble vaccine test system

AIDS vaccine
A new technology speeds up natural antibody “evolution” to create a nimble HIV vaccine test system. (Images: Wikimedia/Pixabay)

An AIDS vaccine able to fight any HIV strain has thus far eluded science. HIV frequently mutates its coat protein, dodging vaccine makers’ efforts to elicit sufficiently broadly neutralizing antibodies.

Yet sometimes HIV-infected people can produce such antibodies on their own. This usually requires years of exposure to the virus, allowing the immune system to modify its antibodies over time to keep up with HIV mutations. But the goal is generally achieved too late in the game to prevent them from being infected.

“Only a small fraction of patients are able to develop broadly neutralizing antibodies, and by the time they do, the virus has already integrated into the genomes of their T-cells,” says Ming Tian, PhD, of Boston Children’s Hospital’s Program in Cellular and Molecular Medicine (PCMM).

Tian is part of a group led by PCCM director Frederick Alt, PhD, that developed a technology to greatly speed up HIV development. Described today in Cell, the group’s method generates mouse models with built-in human immune systems. The model recapitulates what the human immune system does, only much more rapidly, enabling researchers to continuously test and tweak potential HIV vaccines.

Read Full Story | Leave a Comment

BCL11A-based gene therapy for sickle cell disease passes key preclinical test

sickle cell gene therapy coming
(unsplash/Pixabay)

Research going back to the 1980s has shown that sickle cell disease is milder in people whose red blood cells carry a fetal form of hemoglobin. The healthy fetal hemoglobin compensates for the mutated “adult” hemoglobin that makes red blood cells stiffen and assume the classic “sickle” shape.

Normally, fetal hemoglobin production tails off after birth, shut down by a gene called BCL11A. In 2008, researchers Stuart Orkin, MD, and Vijay Sankaran, MD, PhD, at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center showed that suppressing BCL11A could restart fetal hemoglobin production; in 2011, using this approach, they corrected sickle cell disease in mice.

Now, the decades-old discovery is finally nearly ready for human testing — in the form of gene therapy. Today in the Journal of Clinical Investigation, Dana-Farber/Boston Children’s researchers report that a precision-engineered gene therapy vector suppressing BCL11A production overcame a key technical hurdle.

Read Full Story | Leave a Comment

Could targeting specific neurons in the hypothalamus relieve anxiety?

anxiety hypothalamus
(Ichiban Yada/Sketchport.com)

Anxiety disorders are the most common mental illness in the U.S., but lack an ideal treatment. The current drugs, SSRIs and benzodiazepines, have many side effects. More recently developed treatments seek to block corticotropin-releasing hormone (CRH), the classic stress hormone that activates our “fight or flight” response; in people with anxiety, CRH gets activated at the wrong time or too intensely.

But in clinical trials, results have been disappointing: of the eight completed phase II and III trials of CRH antagonists for depression or anxiety, six have been published, with largely negative findings, says Joseph Majzoub, MD, of the Division of Endocrinology at Boston Children’s Hospital.

Rong Zhang, PhD, who works in Majzoub’s research lab, had a hunch that blocking CRH throughout the brain, as was done in these trials, isn’t the best approach. “Blocking CRH receptors all over the brain doesn’t work,” she says. “We think the effects work against each other somehow. It may be that CRH has different effects depending on where in the brain it is produced.”

Today in Molecular Psychiatry, Zhang, Majzoub and colleagues demonstrate that certain neurons in the hypothalamus play a central, previously unknown role in triggering anxiety. When they used genetic tricks to selectively remove the CRH gene from about 1,000 of these neurons in mice, the effect was startling — they erased the animals’ natural fears.

Read Full Story | Leave a Comment

Drug-eluting contact lens offers hope in glaucoma

Daniel Kohane drug-eluting contact lens
Contact lenses ringed with a drug-bearing polymer film provided gradual, sustained drug release in this preclinical study, potentially offering an alternative to eye drops.

Daily medicated eye drops are the first line of treatment for glaucoma, the leading cause of irreversible blindness. The drops relieve pressure in the eye, a significant risk factor for glaucoma. But they’re not ideal: their delivery is imprecise, they can cause stinging and burning and patients often struggle to administer them. Adherence is poor: in one study based on insurance claims data, nearly half of patients who had filled a glaucoma prescription stopped topical glaucoma therapy within six months.

Engineered contact lenses dispensing glaucoma medication gradually could vastly improve adherence, helping hang onto their eyesight longer. In a pre-clinical study of glaucoma published online this week in the journal Ophthalmology, slow-release lenses lowered eye pressure at least as well as daily eye drops containing the drug latanoprost — and, in a higher-dose form, possibly more so.

Read Full Story | Leave a Comment

Acetaminophen does not aggravate young children’s asthma

asthma
A head-to-head comparison with ibuprofen refutes a link between acetaminophen and asthma exacerbations.

Your toddler is screaming in pain. Her forehead is burning. You rush to your local drugstore. What do you get — Tylenol or Motrin? And by the way, she also has asthma.

Recently, many parents have been under the impression that acetaminophen (Tylenol, etc.) may do more harm than good in young children with asthma.

“There’s been a lot of ‘smoke’ about this, based on a lot of retrospective observational data,” says Wanda Phipatanakul, MD, MS, of Boston Children’s Hospital’s Division of Allergy and Immunology.

The studies in question concluded that the common over-the-counter remedy can cause asthma exacerbations. Reviewing these studies, one author concluded, “Until future studies document the safety of this drug, children with asthma or at risk for asthma should avoid the use of acetaminophen.”

The Acetaminophen Versus Ibuprofen in Children with Asthma (AVICA) trial, led by Phipatanakul for the National Heart, Lung and Blood Institute’s AsthmaNet now sets the record straight.

Read Full Story | Leave a Comment

More clinical trials in kids? Nearly half are unfinished or unpublished

pediatric trials clinical trials
Of 559 interventional trials in children, 19 percent were stopped early and 30 percent of completed trials remained unpublished several years later, finds a new study. (Vmenkov/Wikimedia Commons)

Recent laws like the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act are encouraging clinical trials in children. Yet, as with adult trials, these trials commonly stall out or, if completed, remain unpublished several years later, finds a study published online today in Pediatrics.

“Our findings may speak to how commonplace discontinuation and non-publication are in medical research in general,” says Natalie Pica, MD, PhD, a senior resident at Boston Children’s Hospital and the study’s coauthor. “We need to make sure that when children participate in clinical trials, their efforts are contributing to broader scientific knowledge.”

Read Full Story | Leave a Comment

Can asthma be nipped in the bud?

asthma
A multicenter randomized trial is testing omalizumab (Xolair) in wheezy toddlers. (FDA/Wikimedia Commons)

Worldwide, asthma affects an estimated 300 million people, and is expected to surpass 400 million by 2025, according to the World Health Organization. About 1 in 10 U.S. children have asthma, and research shows that the vast majority of them also have allergy. Could that provide a clue to its prevention?

Starting at 2 to 3 years of age, susceptible children start to become sensitized to pollens, mold spores and other airborne allergens. They begin to produce IgE antibodies, which not only trigger allergic reactions but also impair their anti-viral immune responses — potentially leading to more viral infections that can further hasten their progression to asthma.

A multicenter clinical trial, led by Wanda Phipatanakul, MD, MS, of the Division of Allergy & Immunology at Boston Children’s Hospital, now aims to test whether the anti-IgE drug omalizumab (Xolair) can short-circuit this process.

Read Full Story | Leave a Comment