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. …
Over the past decade, mutations to more than 60 different genes have been linked with autism spectrum disorder (ASD), including de novo mutations, which occur spontaneously and aren’t inherited. But much of autism still remains unexplained.
A new study of nearly 6,000 families implicates a hard-to-find category of de novo mutations: those that occur after conception, and therefore affect only a subset of cells. Findings were published today in Nature Neuroscience. …
When infants see or hear something interesting to them, like the sound of a human voice, their heart rate tends to slow down ever so slightly, a sign they’re paying attention. But a recent small study suggests this may not be true for infants at risk for autism.
Researchers led by Katherine Perdue, PhD, of the Laboratories of Cognitive Neuroscience at Boston Children’s Hospital, studied 40 babies who had an older sibling with autism spectrum disorder (ASD). These “baby sibs” are at 20-fold risk for developing autism themselves. For comparison, Perdue and colleagues also studied 48 infants who did not have a sibling with ASD and were therefore at low risk for autism.
At 3, 6, 9 and 12 months of age, the at-risk infants had slower heartbeats than the low-risk infants. When the babies were presented with speech sounds, heart rates slowed less in the at-risk babies than in the low-risk infants.
While none of the at-risk infants, followed until age 2, were later diagnosed with ASD, the researchers believe they may still be at risk for problems such as delayed speech. This may be due to differences in auditory processing. “It might not be autism per se, but it could be something that’s related to communication in some way,” Perdue told Spectrum News.
Attention deficit disorder (ADD), with or without hyperactivity, affects up to 5 percent of the population, according to the DSM-5. It can be difficult to diagnose behaviorally, and coexisting conditions like autism spectrum disorder or mood disorders can mask it.
While recent MRI studies have indicated differences in the brains of people with ADD, the differences are too subtle and MRI too expensive to be a practical diagnostic measure. But new research suggests a role for an everyday, relatively cheap alternative: electroencephalography (EEG). …
A study of tuberous sclerosis, a syndrome associated with autism, suggests a new treatment approach that could extend to other forms of autism.
The genetic disorder tuberous sclerosis complex (TSC) causes autism in about half of the children affected. Because its genetics are well defined, TSC offers a window into the cellular and network-level perturbations in the brain that lead to autism. A study published today by Cell Reports cracks the window open further, in an intriguing new way. It documents a defect in a basic housekeeping system cells use to recycle and renew their mitochondria.
Mitochondria are the organelles responsible for energy production and metabolism in cells. As they age or get damaged, cells digest them through a process known as autophagy (“self-eating”), clearing the way for healthy replacements. (Just this month, research on autophagy earned the Nobel Prize in Physiology or Medicine.)
Mustafa Sahin, MD, PhD, Darius Ebrahimi-Fakhari, MD, PhD, and Afshin Saffari, in Boston Children’s Hospital’s F.M. Kirby Neurobiology Center now report that autophagy goes awry in brain cells affected by TSC. But they also found that two existing medications restored autophagy: the epilepsy drug carbamazepine and drugs known as mTOR inhibitors. The findings may hold relevance not just for TSC but possibly for other forms of autism and some other neurologic disorders. …
One of the hardest parts of developing new treatments for autism spectrum disorder (ASD) is that almost every patient has a different combination of environmental and genetic risk factors. This suggests that every patient could take a unique path to their diagnosis. It is hard to come up with a single treatment that will help patients with fundamentally different root causes of ASD.
One way to approach this problem is to look for ways to cluster sub-types of autism for clinical trials, based on genetic risk factors or the types of neural circuits that are affected. If circuit dysfunction could be monitored and diagnosed easily in patients, it might be possible to develop treatments to reverse the dysfunction that cut across genetic and environmental causes of ASD. That is the hope of research on well-defined “syndromic” causes of autism such as tuberous sclerosis complex, Fragile X syndrome and Rett syndrome.
Accelerating research collaborations to design clinical trials for children with brain disorders, including ASD, is a major mission of Boston Children’s Hospital’s Translational Neuroscience Center (TNC).A recent study in Translational Psychiatry, led by Mathew Alexander, PhD, in the Boston Children’s lab of Lou Kunkel, PhD, in collaboration with the TNC and Pfizer, is a prime example. It suggests that patients with Duchenne muscular dystrophy (DMD) may constitute another subset of ASD patients — one that could benefit from phosphodiesterase (PDE) inhibitors, a family of drugs including Viagra. …
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. …
What makes children with autism tick, and how can we help them function better socially? That’s the focus of research in the lab Susan Faja, PhD, at Boston Children’s Hospital.
The GAMES project seeks to build social skills in children with autism spectrum disorder (ASD) by building cognitive skills, specifically executive functioning. Through computer games and coaching, Faja hopes strengthen kids’ ability to plan, inhibit behavior, manage complex or conflicting information and shift flexibly between different rules or situations. She believes executive function training will help children with ASD better understand other people’s perspectives and act more appropriately in social situations.
Faja is also interested in biomarkers that indicate whether interventions are working, including brain EEG recordings and eye tracking. She’s using these tools to learn what visual information kids with ASD are attending to and how their brains respond to social information.
“I think the thing that really makes my lab unique is that we are looking at both neuroscience and intervention at the same time,” says Faja. “We take information from the neuroscience literature about how the brain develops, and we look for ways to apply that to developing new treatments.”
Eleven-year-old Lyle has autism and doesn’t speak, but his mother is used to reading his nonverbal cues. He prefers a routine, but has always been a generally cheerful child who enjoys school and playing with his little sister.
Several weeks before I met Lyle (not his real name), his mother observed a dramatic shift. He was agitated, at times hitting his head against the wall, not receiving his typical sunny reports from school. …
Disease-causing mutations can be incredibly subtle: Sometimes a single-letter change in a gene or a so-called somatic mutation (affecting only some of the body’s cells) can be enough. Researchers report this week in Neuron that both kinds of mutations — easily missed on standard blood and saliva testing — play a role in autism spectrum disorder (ASD).
Scientists have suspected a role for these mutations in brain disorders, but the technology to find them has only recently come online. Sampling brain tissue is the most likely way to find them, but brain biopsies aren’t something you do every day.