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.
Thomas is feeding virtual bananas to virtual monkeys. If the banana is yellow, he presses the computer’s arrow key to feed it to the monkey. If it’s brown, he’s supposed to just wait for the next banana. “Good job, you really watched carefully,” says Susan Faja, PhD, who’s coaching him through the task.
In the next round, Thomas has to throw bananas in the trash—but only the brown ones. “Oops, I threw a good banana away!” Thomas exclaims. “No worries,” Faja reassures him, “let’s try and remember the new rule on the next one.”
Being able to inhibit impulses—even small ones—is one aspect of what’s called executive function, a set of cognitive skills that allow us to manage complex or conflicting information, solve more nuanced problems and fine-tune our behavior. Executive function also includes the ability to plan, hold information in mind, and shift flexibly between different rules in different situations. And Faja thinks that strengthening executive function could help children with autism spectrum disorder (ASD) function better socially. …
Reports 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.
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. …
Rett syndrome, a neurodevelopmental disorder affecting mostly girls, takes away the ability to speak, and this makes the condition hard to reliably measure and assess. But children with Rett syndrome also display distinctive hand movements or stereotypies, including hand wringing, clasping and other repetitive hand movements, visible in many of these videos. With help from a grant from Boston Children’s Hospital’s Innovation Acceleration Program, researchers are transforming these hand movements into an assessment tool.
Until now, there has been no quantitative measure for monitoring Rett hand movements. Adapting commercially available wearable sensor technology, biomedical engineering researcher Heather O’Leary has created a bracelet-like device not unlike Fitbit, another wearable accelerometer used to monitor exercise activity levels. …