The time Anna stayed up all night

Almost precisely a decade ago, a young Atlanta lawyer named Anna was returning to work, after being treated for an extraordinary sleep disorder. Her story has been told here at Emory and by national media outlets. Fast forward a decade to Idiopathic Hypersomnia Awareness Week 2018 (September 3-9), organized by Hypersomnolence Australia. What this post deals with is essentially the correction of a date at the tail end of Anna’s story, but one with long-term implications Read more

Mini-monsters of cardiac regeneration

Jinhu Wang’s lab is not producing giant monsters. They are making fish with fluorescent hearts. Lots of cool Read more

Why is it so hard to do good science?

Last week, Lab Land put out a Twitter poll, touching on the cognitive distortions that make it difficult to do high-quality science. Lots of people (almost 50) responded! Thank you! We had to be vague about where all this came from, because it was before the publication of the underlying research paper. Ray Dingledine, in Emory’s Department of Pharmacology, asked us to do the Twitter poll first, to see what answers people would give. Dingledine’s Read more

autism

Oxytocin receptor levels predict comforting behavior in prairie voles

Different levels of a receptor for a hormone involved in social bonding may explain individual variation in offering comfort during stressful situations. Like humans, animals console each other in times of distress: monkeys hug and kiss, and prairie voles groom each other.

James Burkett, PhD

James Burkett, PhD

Emory postdoc James Burkett described his research on voles at a press conference on “The Neuroscience of Emotion and Social Behavior” at the Society for Neuroscience meeting in San Diego on Sunday. Here are Video (Burkett’s part is roughly from 4:50 to 9:00) and the scientific abstract.

Burkett’s presentation, on oxytocin-dependent comforting behavior in prairie voles, outlined an extension of his graduate work with Larry Young at Yerkes National Primate Research Center, which was published in Science in January 2016 and impressed oxytocin skeptic Ed Yong. Burkett, now in Gary Miller’s laboratory at Rollins School of Public Health, also masterminded a Reddit “Ask me anything” in February.

The rest of the Society for Neuroscience press release:

Previous research indicates oxytocin—a hormone that promotes social and maternal bonding—acts in the anterior cingulate cortex (ACC) of the prairie vole brain to encourage consoling behavior. In humans, the ACC activates when people see others in pain. Some degree of personal distress motivates comforting behaviors, but too much actually makes animals (including humans, chimpanzees, and rats) less likely to offer comfort.

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Revisiting landmark folate-autism study

Geneticist Joe Cubells is doing some monumental work re-examining a Chinese study of folic acid supplementation during pregnancy and its impact on autism risk. He is also the Medical Director at the Emory Autism Center. Please see SFARI to check it out.

 

 

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Socialization relative strength in fragile X longitudinal study

A study published in Pediatrics this week tracks “adaptive behavior” as children and adolescents with fragile X syndrome are growing up. This is the largest longitudinal study to date in fragile X, which is the leading inherited cause of intellectual disability and the leading single-gene risk factor for autism spectrum disorder.

Adaptive behavior covers a range of everyday social and practical skills, including communication, socialization, and completing tasks of daily living such as getting dressed. In this study, socialization emerged as a relative strength in boys with fragile X, in that it did not decline as much as the other two domains of adaptive behavior measured: communication and daily living skills.

The lead author of the paper is Cheryl Klaiman, formerly of the Stanford University Center for Interdisciplinary Brain Sciences, now senior psychologist at Marcus Autism Center.

The “socialization as relative strength in fragile X” findings meshes with a growing awareness in the autism field, summarized nicely here by Jessica Wright at the Simons Foundation Autism Research Initiative, that fragile X syndrome symptoms are often distinct from those in autism spectrum disorder.

One key distinction between the disorders, for example, is in social interactions. Children with autism and those with fragile X syndrome both shy away from social contact, have trouble making friends and avert their gaze when people look at them.

But children with fragile X syndrome often sneak a peek when the other person turns his back, researchers say. Children with autism, in contrast, seem mostly uninterested in social interactions.

“Children with fragile X syndrome all have very severe social anxiety that plays a big role in the perception that they have autism,” says Stephen Warren, professor of human genetics at Emory University School of Medicine in Atlanta. “They are actually interested in their environment; they are just very shy and anxious about it.”

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Personalized molecular medicine part 2

This is a continuation of the post from last week on the early-onset epilepsy patient, whom doctors were able to devise an individualized treatment for. The treatment was based on Emory research on the molecular effects of a mutation in the patient’s GRIN2A gene, discovered through whole exome sequencing.*

For this patient, investigators were able to find the Ray Ban Baratas cause for a previously difficult to diagnose case, and then use a medication usually used for Alzheimer’s disease (memantine) to reduce his seizure frequency.

Last week, I posed the question: how often do we move from a disease-causing mutation to tailored treatment? Read more

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Fragile X clinical trial update

A recent issue of Emory Health magazine had an article describing the progress of clinical trials for fragile X syndrome, the most common inherited cause of intellectual disability. The article included interviews with the parents of a boy, Samuel McKinnon, who is participating in one of the phase III clinical trials here at Emory.

Last week, results for the phase II study for the same medication were published in Science Translational Medicine. The drug, called STX209 or arbaclofen, is one of the first designed to treat the molecular changes in the brain caused by fragile X syndrome. STX209 shows some promise in its ability to reduce social withdrawal, a key symptom of fragile X syndrome.

In one case, a boy was able to attend his birthday party for the first time in his life. In the past, he had been too shy and couldn’t tolerate hearing people sing Happy Birthday to You, the study’s lead author Elizabeth Berry-Kravis, MD, PhD from Rush University, told USA Today.

These results have generated excitement among autism researchers and specialists, because a fraction of individuals with fragile X mutations have autism and the same drug strategy may be able to address deficits in other forms of autism.

Some caveats:
1. Autism and fragile X are not the same thing.
2. This was a phase II study, the phase III results are yet to come.
3. The study authors are up front about saying that the “primary endpoint” (irritability) showed no difference between drug and placebo.

A team led by Emory genetics chair Steve Warren identified the gene responsible for fragile X in 1991, and Emory scientists have been important players in figuring out its effects on the brain.

Warren and colleague Mika Kinoshita are co-authors on a companion paper in STM on treatment of fragile X mice. A thoughtful review piece in the same issue of STM lays out current issues in developing therapies for “childhood disorders of the synapse.”

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Autism linked to hundreds of spontaneous genetic mutations

Emory genetic researchers Daniel Moreno De Luca, Christa Lese Martin and David Ledbetter were part of a team that produced a landmark result in autism genetics. The team identified hundreds of regions of the genome where spontaneous mutations are implicated in autism. Spontaneous mutations are those that arise for the first time in an individual, rather than being inherited from parents.

Christa Lese Martin, PhD

The team was led by Matthew State at Yale, and their results were published in the journal Neuron. Moreno De Luca discussed the topic in Spanish on a recent edition of the NPR program Science Friday. The June 10 segment was focused on autism genetics.

The team made an intriguing finding on a segment of chromosome 7. Deletion of the region is associated with Williams syndrome, where individuals can exhibit “striking verbal abilities, highly social personalities and an affinity for music.” Duplication of the same region, they found, is associated with autism.

Daniel Moreno De Luca, MD MSc

Companion studies also shed light on the question of why boys are more likely to develop autism than girls, and begin to outline a network of genes whose activity is altered in the brains of individuals with autism.

Ledbetter is now chief scientific officer at Geisinger Health in Pennsylvania.

 

 

 

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Links between autism and epilepsy

An article in the April 2011 issue of Nature Medicine highlights the mechanistic overlap between autism and epilepsy.

By studying how rare genetic conditions known to coincide with both epilepsy and autism—such as Rett syndrome, fragile X syndrome and tuberous sclerosis—unfold at an early age, neuroscientists are finding that both disorders may alter some of the same neural receptors, signaling molecules and proteins involved in the development of brain cell synapses.

Gary Bassell, PhD

Emory cell biologist Gary Bassell and his colleagues have been taking exactly this approach. Recently they published a paper in Journal of Neuroscience, showing that the protein missing in fragile X syndrome, FMRP, regulates expression of an ion channel linked to epilepsy. This could provide a partial explanation for the link between fragile X syndrome and epilepsy.

The Nature Medicine article also mentions a drug strategy, targeting the mTOR pathway, which Bassell’s group has been exploring with fragile X syndrome.

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Inclusive Environment Helps Children with Autism Spectrum Disorders Learn

The Monarch Program

The Monarch School Program is dedicated to providing information and resources to families and school systems throughout Georgia for the education of K-12 students with autism / autistic spectrum disorder.

Educators have known for a long time that children with Autism Spectrum Disorder (ASD) can learn a lot by being in a classroom with typical children. Inclusion (educating students within the general education classroom) gives children with special needs the opportunity to learn in a natural environment and the opportunity to learn social skills from interacting with their classmates. In addition, Inclusion can eventually lead to greater acceptance of these children in the community.

Unfortunately, teachers are not always trained how to help children with special needs function in a typical classroom, nor in ways to ensure successful imitation of the positive role models.

“Teachers do not necessarily have the specific training required to teach these children yet, too often, the children with ASD are placed in the classroom with the expectation that the teacher, or the student, will learn to adapt,” says Sheila Wagner, M.Ed., assistant director of the Emory Autism Center. “Without the training, many times the student faces failure, when success was the goal.”

In order to provide some guidance to the school system, the Emory Autism Center received a grant from the Childhood Autism Foundation (CADEF) in 1994 to develop a program that would address Inclusive Education for students with ASD.  With the help of CADEF, the Monarch Program was created. The program implemented a nationally recognized Inclusion Project that has reached hundreds of students with ASD, thousands of teachers through on-site technical assistance and training, and assisted thousands of typical students in learning about the autism spectrum and children with different behaviors and abilities.

“The Monarch Program has grown to provide school systems with a network of support from curriculum training, to teacher and home/school collaboration, to consultations and social skills curriculum,” says Wagner, who serves as the Program Manager of the Monarch School-Age Program at Emory.

“Because of the Monarch Inclusion Project, students with ASD are increasingly able to enjoy exposure to typical students, and teachers are offered some guidance in providing a positive classroom experience.”

Wagner began her experience in the field of autism more than 30 years ago and has published three books on inclusive programming for students with ASD, as well as a brochure on Asperger’s syndrome, and a chapter in Grandin & Attwood’s book Aspergers and Girls.

The Emory Autism Center is a component of the Department of Psychiatry and Behavioral Sciences at Emory University School of Medicine. The program was opened in 1991 as a public, private and University collaboration. Since opening, the Emory Autism Center has become a national model for diagnosis, family support and innovative treatment, as well as a vital source of professional training.

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New drug strategy against fragile X

Even as clinical trials examining potential treatments for fragile X syndrome gain momentum, Emory scientists have identified a new strategy for treating the neurodevelopmental disorder.

In a paper recently published in Journal of Neuroscience, a team led by cell biologist Gary Bassell shows that PI3 kinase inhibitors could restore normal appearance and levels of protein production at the synapses of hippocampal neurons from fragile X model mice. The next steps, studies in animals, are underway.

“This is an important first step toward having a new therapeutic strategy for fragile X syndrome that treats the underlying molecular defect, and it may be more broadly applicable to other forms of autism,” he says.

A recent Nature Biotechnology article describes pharmaceutical approaches to autism and fragile X.

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Quirky little prairie voles hold answers

Larry Young, PhD

So says Larry Young, PhD, chief of the Division of Behavioral Neuroscience and Psychiatric Disorders at the Yerkes National Primate Research Center, Emory University.

Young, who is world-renowned for his work on the role of neuropeptides in regulating social behavior, uses voles to investigate the neurobiological and genetic mechanisms underlying social behavior. Using the monogamous prairie vole (vs. the promiscuous meadow vole) as a model organism, Young and his research team identified the oxytocin and vasopressin receptors as key mediators of social bonding and attachment. In addition, they are examining the consequences of social bond disruption as a model of social loss-induced depression.

This work has important implications for developing novel treatment strategies for psychiatric disorders associated with social cognitive deficits, including autism spectrum disorders and schizophrenia.

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