Sunday, May 1, 2016

Huddle Up 2016 Scores a Touchdown!

We were incredibly lucky to have one of the most beautiful days of the spring for the 6th annual Huddle Up for Autism at Lincoln Financial Field on April 17th!

Each year since 2009, the Philadelphia Eagles have partnered with CHOP's Center for Autism Research (CAR) to transform the stadium and field into a carnival-like atmosphere designed specifically with the needs of individuals on the autism spectrum in mind. This year's "sold-out" event attracted more than 3,000 guests and was free of charge to families. Huddle Up is also a fundraiser, and raised more than $40,000 for CAR programs and research!

Families were invited to explore the stadium locker rooms, run drills with Temple and Eagles players, run onto the field through the Eagles “helmet tunnel", kick a field goal, and play a giant game of inflatable life-sized bowling on the field!  Inside, sensory stations, music therapy, and quiet rooms were available to families who needed a break from the action, and child specialists from CAR were on hand to lend assistance when needed. In addition to fun and games, the event provided an opportunity for families to learn about resources and research opportunities with CAR, and to speak with some of the nation's foremost autism specialists and researchers in an informal setting.

"It can be hard for people with autism to enjoy a regular game day at the stadium. The noise, crowds and excitement can be overwhelming. So We pull out all the stops at Huddle Up, so these fans have a chance to meet some of the Eagles players, cheerleaders and SWOOP, and to roam the stadium in a supportive environment," said Robert T. Schultz, PhD, CAR's director. "We’re grateful for the Eagles’ ongoing commitment to supporting CAR’s mission of finding the causes and treatments for autism spectrum disorders, educating families, and training professionals in the field.”
We would especially like to recognize and THANK our top three fundraisers:
  1. Help Rock Autism raised $3,000 and received four pre-game field passes and four tickets to a Philadelphia Eagles home game for the 2016-2017 season!

  2. Team Anthony raised $2,100 and received four VIP Passes to the Philadelphia Eagles Training Camp at the NovaCare Complex!

  3. Team Liam raised $1,621 and received an authentic autographed Connor Barwin Jersey!
We  look forward this event to every year, and we truly think this year was the best one yet! Thank you to our amazing volunteers and the incredible Eagles staff who go above and beyond to make this a such a great experience for everyone who attends! 
Check out this photo gallery for more of our favorite shots from the day.  We also encourage you to post any photos you'd like to share on CAR’s Facebook page!
If you haven't made a donation to CAR and would like to do so, you can visit Huddle Up for Autism's donation page here

Friday, April 8, 2016

New CHOP Research Study Tests Brain’s Response to Single Dose of Arbaclofen (STX209)

Many in the autism community are familiar with the trial drug STX209, also called arbaclofen, which affects a chemical system called GABA. In 2010, clinical trials were launched to evaluate whether arbaclofen might become the first medication to treat core symptoms of social communication impairment and repetitive behavior in autism spectrum disorder (ASD).

Among a small subset of participants in these early clinical trials, the drug showed promise for treating secondary outcomes- namely, some of the social symptoms that accompany autism spectrum disorder (ASD) and fragile X syndrome (FXS).

In order to declare a medication trial a success, drug developers need to be able to predict what the drug will do and then show that it performs as promised. While a small set of patients did see improvements- particularly in the area of social withdrawal- researchers weren’t able to predict which children would see positive treatment effects or what those positive effects would be. This is a common challenge in studying ASD, since symptoms can vary so widely in their expression. As a result, in 2013, the drug’s manufacturer discontinued a clinical trial of the drug, citing a lack of funding and unproven efficacy for the drug’s primary outcomes in treating ASD and FSX.

For the families whose children did display social and behavioral improvements during the drug trial, it was disappointing to receive the news that the study was discontinued and that the manufacturer could no longer afford to keep manufacturing the drug.

Researchers remain interested in finding ways to test the effects of the very limited quantities of arbaclofen that remain. To that end, CHOP was recently approved to conduct a brain imaging study that will use magnetoencephalography (MEG) and magnetic resonance Imaging (MRI) to determine whether a single dose of Arbaclofen results in any changes in brain activity in boys aged 14-17 with ASD. Whereas the initial studies just looked at behavioral outcomes, the CHOP research team is trying to explore the brain’s response to the drug. Funding for the new study comes from Clinical Research Associates, a subsidiary of the Simons Foundation.

“The study will allow us to look at a very specific mechanism of STX209,” said the study’s lead investigator, Timothy Roberts, PhD, Oberkircher Family Chair in Pediatric Radiology at The Children's Hospital of Philadelphia. “By testing the effects of the drug in single doses, we will be able to determine if it does indeed have a fast effect on changing brain activity, and if those changes in brain activity depend on the dose of the medication.” Roberts followed up; “Moreover, by examining the intricacies of brain activity with MEG before administering each dose, we hope to find biologically-based signs that predict whose brain might respond and whose might not, and thus provide a stratification basis for inclusion in any future trials.”

Incremental findings like this could help the scientific community determine whether there is a case for resuming clinical trials focused on arbaclofen.

More information about the study and how to participate is available here.

For more about the history of the arbaclofen trials and recent studies of the drug in animal models, check out this podcast from the Autism Science Foundation.

Wednesday, January 27, 2016

CHOP Researchers Identify Gene That Plays Important Role in Autism & Other Neuropsychiatric Conditions

A team of researchers led by Tara Wenger, PhD of The Children's Hospital of Philadelphia's Center for Autism Research (CAR) have found that genetic mutations in a specific family of genes – the “metabotropic glutamate receptors” (mGluRs) – play a significant role in a person’s risk for autism spectrum disorder (ASD). One mGluR gene in particular- RANBP1- was the focus of a study published this month in the Nature journal Scientific Reports. The mGluR gene network typically contains two copies of RANBP1; however, in children who were missing one of those RANBP1 genes, the risk of autism increased dramatically.

Previous studies have shown that RANBP1 contributes to “syndromic autism”- a form of ASD caused by genetic mutations that lead to complex medical problems. Syndromic ASD, which includes 22q11.2 Deletion Syndrome, Fragile X Syndrome, and Tuberous Sclerosis, accounts for about 20% of all ASD cases and  are frequently more severe forms of ASD.

The new CAR
study confirms the important role of mGluR genes in other neuropsychiatric conditions, such as attention-deficit hyperactivity disorder (ADHD), in addition to autism. Moreover, this mGluR family of genes contains hints about how several well-known environmental factors may cause ASD, including prenatal exposure to thalidomide. The scientists say these findings pave the way for developing precision treatments targeted to those who carry this genetic variation.

“This is another step in of a series of genetic findings that shine a spotlight on select aspects of early neurodevelopment that contribute most to ASD,” said Robert Schultz, PhD, Director of the CAR. “At CHOP we are extremely fortunate to be able to convene the resources and expertise of the
Center for Applied Genomics (CAG), the 22q and You Center, and CAR in order to examine complex genetic questions – spanning multiple diagnoses- in order to tease out important interactions among genetic and environmental factors that increase a child’s risk of developing ASD, and in turn develop targeted treatments. There are only a few places in the world positioned to do this type of research.”

For this study, scientists analyzed DNA from more than 500 children with ASD. They searched for copy number variations (CNVs) within the mGluR gene network, since previous studies have shown that CNVs within this mGluR “gene family” occur more frequently in children with ASD than in other children. The research team discovered that children with ASD who also had CNVs within the mGluR network were far more likely to have the syndromic type of ASD, compared to those without CNVs in mGluR.

The study team also compared the ASD cohort to a separate set of 75 children with 22q11.2 deletion syndrome, 25 of whom also had ASD. All 75 were already missing RMBP1, because that gene is contained in the deleted region of their chromosome.  But if they had a “second hit”—either a deletion or a duplication of another mGluR gene outside that region—they were much more likely to have autism than children with the deletion syndrome who didn’t have that second hit.
Combining these findings, the research team concluded the RANBP1 gene is a significant genetic factor in some forms of ASD, and the greater number of mGluR genes affected, the greater the chances of the person developing ASD. “The mGluR variants we identified may be important in identifying those patients who are most likely to respond to new treatments,” said Hakon Hakonarson, MD, PhD, Director of the Center for Applied Genomics at CHOP. “As such, this could be the basis for one of the first examples of a precision medicine focus in drug development for complex disease.”
This study, entitled "The Role of mGluR CopyNumber Variation in Genetic and Environmental Forms of Syndromic AutismSpectrum Disorder”, was published January 19th in Scientific Reports. The study was led by Tara Wenger, MD, PhD of CHOP’s Center for Autism Research and Hakon Hakonarson, MD, PhD, director of CHOP’s Center for Applied Genomics. Co-authors included Robert Schultz,PhD, director of CHOP’s Center for Autism Research and Donna McDonald-McGinn, MS, CGC, program director of CHOP’s 22q and You Center. Find more information about these research findings in the accompanying press release. 

Switching Lenses: A Shift in Perspective Led Researchers to Unexpected Results About Face-Processing in ASD

Humanity seems to be “hard-wired” to pay attention to faces and facial expressions. Zeroing in on faces (rather than other body parts or objects) and being able to differentiate between people’s identities or expressions is one of the first skills developed during infancy; and differences in social attention appear to be one of the earliest observable signs of autism.
Because reduced attention to and interest in social information is a prevalent symptom of ASD, many studies have focused on comparing two groups - those on the spectrum vs. those with typical development - to search for differences in how they prioritize faces compared with other objects in the environment. However, no one had studied individual differences along the continuum of “face expertise”, without taking diagnostic labels into account. A group of CAR scientists led by Julia Parish-Morris, PhD, and Coralie Chevallier, PhD (now at INSERM), believed that ignoring diagnostic categories in favor of a more “dimensional approach” might improve our understanding of how humans develop their facial recognition skills and might also shed light on how differences in attentional biases or motivation to look at faces might influence the development of social skills.
For their study, the researchers enrolled 110 children between the ages of 6 and 17 (50 typically developing and 60 with ASD). The children participated in a series of scientifically validated tests, including Let’s Face It! - a computer game-based intervention designed help teach facial processing skills- to assess their ability to recognize both a person’s identity and perceive differences in facial expressions. They also watched short videos showing faces and objects, while their eye movements were tracked to measure gaze and attention. The team assessed each child’s behavior and social using the Social Communication Questionnaire (SCQ).
“We were surprised to find that, overall, children with ASD and their typically developing peers spent a similar amount of time looking at faces and objects,” explained Dr. Parish-Morris.
Interestingly, children who paid more attention to facial information were better able to differentiate between face identities and facial expressions in the Let’s Face it game, and so did children who performed better on the SCQ.

According to Dr. Parish-Morris, “The connection between attention to faces and face processing skill held regardless of whether or not the participant had autism. This suggests that face processing is truly dimensional and linked to underlying differences in social attention or motivation.” The Social Motivation Theory of autism suggests that while these differences might start small, they could have a snowball effect on face processing skill over developmental time.

Using a dimensional approach to assess social processing in autism is gaining favor across multiple areas of mental health research, and is consistent with a growing trend to think of ASD in terms of neurodiversity. Just as autism displays itself across a wide spectrum of symptoms and characteristics, it can be helpful for researchers to take a spectrum-approach as well, rather than adhering to strict diagnostic categories at the outset.

Shifting the lens through which we study ASD creates the potential for new pathways to understanding the variability that makes the diagnosis so challenging. Parish-Morris and her colleagues are interested in further exploring  the relationship between social interest, social motivation, and a person's  ability to identify and interpret faces as a potential area of interest for developing effective skill-building tools.

Friday, December 11, 2015

New Findings related to Attention and Gaze Give Us Clues to Differences in Social Development for Individuals on the Autism Spectrum

Difficulty interpreting social information is one of the defining characteristics of autism spectrum disorders (ASD), but  there is still a lot we don't understand about the underlying causes of some of these social differences.  A key aim of our research at CAR is to advance our understanding about the origins of difficulty with processing social information that is so common in ASD. This knowledge will help us devise better therapies.

There are four key areas of social development that are commonly disrupted by autism which, when taken together, describe much of what it means to have ASD. They include (1) theory of mind, or the ability to understand the thoughts, beliefs, or intentions of others (2) joint attention, or the inclination to pay attention to the same object of interest as someone else, as it relates to speech development; (3) social perception, or the ability to recognize facial expressions or speech inflections; and (4) social attention, or the tendency to prioritize important social information, such as an angry or distressed facial expression, over non-social information, such as pictures on a wall or furniture in a room.

In this the next couple of blog posts, we take you on a deeper dive into a group of CAR studies that are beginning to unlock some answers as to how social attention develops in autism.

"Why on earth would I want to do that?": The Basics of Social Motivation in Autism Spectrum Disorders

New CAR Research: Attention and Gaze Hold Clues to Social Development in Autism