Stories about: Rett syndrome

A biomarker for Rett syndrome: Measuring hand movements

Rett syndrome stereotypies bracelet Q-sensor curveRett 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.

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Rett syndrome sees glimmer of hope in Phase I trial

Hope for Rett syndrome?This post is the first in a two-part series on clinical trials in autism spectrum disorders. Read part 2.

In the world of neurodevelopmental disorders, an exciting trend is the emergence of specific molecular targets and treatments through genetic research. A case in point is IGF-1 therapy for Rett syndrome, a devastating disorder in girls that affects their ability to speak, walk, eat and breathe. It causes autism-like behaviors, intellectual disability and repetitive hand-wringing movements—a hallmark of the disorder.

A Phase I trial, published this week in the Proceedings of the National Academy of Sciences Early Edition, has modest but consistent results suggesting improvements in some salient features of the disorder.

Current treatments for Rett syndrome address only the symptoms and comorbidities, such as seizures, anxiety and scoliosis, but not the disease itself. But in 2007, findings in a mouse model (which even replicated the hand-wringing) changed how scientists think about Rett and other neurodevelopmental disorders, previously thought to be untreatable.

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Visionary research on Rett syndrome

Mice with the mutation causing Rett syndrome (middle panel) have an excess of inhibitory connections as compared with normal mice (left panel) and mutated mice reared with no visual stimulation (right panel). Inhibitory connections were also reduced by manipulating the NMDA receptor, restoring a more normal balance of inhibition/excitation.

Research just published in Neuron offers some interesting clues about Rett syndrome, a tragic disease that causes initially healthy girls to lose their ability to speak and to develop motor and respiratory problems. Working with a mouse model, the Boston Children’s Hospital lab of Michela Fagiolini, PhD, explored how the causative mutations, affecting the MECP2 gene, disrupt brain circuitry and function. The team found that the circuit damage can be undone by targeting the NMDA receptor, tipping the brain toward the right balance of inhibition and excitation. They’re now exploring possible pharmaceutical approaches.

The study also suggests that changes in the visual system are a tip-off to what’s going on in the brain as a whole.

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A match made in heaven: The Children’s/MIT Research Enterprise

Crossing the river has had benefits that go back decades (Roger Wollstadt/Flickr, 1975)

It’s inspiring to see what happens when a hospital dedicated to providing the best treatments for children partners with a world-class technology and engineering institution.  Children’s Hospital Boston and MIT have embarked upon an exciting program of collaboration and cross-fertilization in research, teaching and mentoring. The goal is to connect outstanding disease-oriented research with cutting-edge innovation and technologies, taking our ability to care for children to a new level while training the next generation of clinicians and scientists.

The historical ties between Children’s and MIT run deep. Individual scientists and clinicians have teamed up to design new medical devices; to identify gene mutations that underlie cancer and disorders of development; to create new approaches to drug delivery using slow-release polymers to extend medication efficacy;

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Why does brain development diverge in autism?

Many autism spectrum disorders (ASDs) are marked by apparently normal development in infancy followed by a tragic loss of cognitive, social and language skills starting at 12 to 18 months of age. ASDs are increasingly seen as a disorder of synapses, the connections between neurons that together form brain circuits.

What hasn’t been clear is why children with ASDs go off the normal trajectory after meeting their early developmental milestones. But now there may be a hint of an explanation.

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Neurogenetic disorders: Dreaming the impossible dream

People with autism and most other disorders of brain development have never had medications to treat their core behavioral and cognitive symptoms. The best they can get are drugs targeting secondary problems, like irritability or aggression. But now, a new wave of clinical trials, such as the one we posted about yesterday for Rett syndrome, aims to change this.

In the last decade, scientists have discovered many of the molecular pathways in genetic disorders that can impair cognition and place a child on the autism spectrum—such as tuberous sclerosis complex, Rett syndrome, Fragile X syndrome and Angelman syndrome. These discoveries are suggesting targets for drug treatment, and is changing how these conditions—and perhaps neurodevelopmental disorders generally—are viewed.

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Can Rett syndrome be reversed?

Khwaja evaluates a young girl with Rett syndrome, the leading known genetic cause of autism in girls.

In 2007 an extraordinary paper was published, suggesting that developmental disorders, including autism spectrum disorders, aren’t necessarily a done deal. Working with a mouse model of Rett syndrome, a disorder causing severe cognitive, motor and language problems and autistic behaviors, mostly in girls, researchers in Scotland restored the function of MeCP2, the mutated gene. The mice showed a striking reversal of their neurologic symptoms.

The paper has had an impact around the world, changing how scientists think about disorders that have been thought to be untreatable.

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