Featured Research

from universities, journals, and other organizations

Medication effective in treating social withdrawal in Fragile X and potentially autism patients

Date:
September 19, 2012
Source:
Rush University Medical Center
Summary:
An investigational compound that targets the core symptoms of fragile X syndrome is effective for addressing the social withdrawal and challenging behaviors characteristic of the condition, making it the first such discovery for fragile X syndrome and, potentially, the first for autism spectrum disorder, a study has found.

An investigational compound that targets the core symptoms of fragile X syndrome is effective for addressing the social withdrawal and challenging behaviors characteristic of the condition, making it the first such discovery for fragile X syndrome and, potentially, the first for autism spectrum disorder.
Credit: iStockphoto/Marcin Pawinski

An investigational compound that targets the core symptoms of fragile X syndrome is effective for addressing the social withdrawal and challenging behaviors characteristic of the condition, making it the first such discovery for fragile X syndrome and, potentially, the first for autism spectrum disorder, a study by researchers at Rush University Medical Center and the University of California, Davis MIND Institute has found.

The finding is the result of a clinical trial in adult and pediatric subjects with fragile X syndrome. It suggests, however, that the compound may have treatment implications for at least a portion of the growing population of individuals with autism spectrum disorder, as well as for those with other conditions defined by social deficits. The study is published online September 19 in the journal Science Translational Medicine.

"There are no FDA-approved treatments for fragile X syndrome, and the available options help secondary symptoms but do not effectively address the core impairments in fragile X syndrome," said Dr. Elizabeth Berry-Kravis, the lead author of the article. "This is the first large-scale study that is based on the molecular understanding of fragile X syndrome and, importantly, suggests that the core symptoms may be amenable to pharmacologic treatment." Berry-Kravis is professor of Pediatrics, Neurological Sciences, and Biochemistry at Rush.

The "first-in-patient" drug trial was led by Berry-Kravis and Dr. Randi Hagerman of the UC Davis MIND Institute. It examined the effects of the compound STX 209, also known by the name Arbaclofen. The study was conducted collaboratively with Seaside Theraputics, a Cambridge, Mass., pharmaceutical company, that is focused on translating bench research on fragile X and autism into therapeutic interventions. Seaside Therapeutics produces the compound.

"This study shows that STX 209 is an important part of the treatment for fragile X syndrome, because it improved symptoms in those with significant social deficits or autism as well as fragile X syndrome," said Hagerman, who is the medical director of the MIND Institute. "Additional studies also are suggesting that STX 209 can be helpful for autism without fragile X syndrome. Until now, there have been no targeted treatments available for autism. This appears to be the first."

Fragile X syndrome is the most common known cause of inherited intellectual impairment, formerly referred to as mental retardation, and the leading known single-gene cause of autism. Social impairment is one of the core deficits in both fragile X and autism. The U.S. Centers for Disease Control and Prevention (CDC) estimates that about 1 in 4,000 males and 1 in 6,000 to 8,000 females have the disorder. An estimated 1 in 88 children born today will be diagnosed with autism, according to the CDC.

"This study will help to signal the beginning of a new era of targeted treatments for genetic disorders that have historically been regarded as beyond the reach of pharmacotherapy," Berry-Kravis said. "It will be a model for treatment of autism, intellectual disability and developmental brain disorders based on understanding of dysfunction in brain pathways, as opposed to empiric treatment of symptoms. We hope mechanistically-based treatments like STX209 ultimately will be shown to improve cognitive functioning in longer-term trials."

Studies in mice genetically engineered to exhibit features of fragile X, including social impairment, have suggested that the behavioral abnormalities in fragile X result from deficiencies in the neurotransmitter gamma-amino butyric acid (GABA). Decreased GABA has been observed in a mouse model of fragile X in many areas of the brain including the hippocampus, and has been hypothesized to be a basis of the social anxiety and avoidance characteristic of fragile X sufferers, the study says.

Arbaclofen is an agonist for gamma-amino butyric acid type B, or GABA-B, receptors. An agonist is a chemical that effectively combines with a receptor on a synapse to effect a physiologic reaction typical of a naturally occurring substance. Anxiety-driven repetitive behavior and social avoidance have been reduced in fragile X-engineered mice treated with arbaclofen. The current, first-of-its-kind study investigated whether Arbaclofen would produce similar results in human subjects.

The double-blind, placebo-controlled clinical trial initially recruited 63 subjects at 12 sites across the United States for the research, conducted between December 2008 and March 2010. The participants ranged in age from 6 to 39 years. Of the initial participants, 56 completed the clinical trial. There were no withdrawals related to drug tolerability. The majority of the subjects were treated with what was assessed as the optimum tolerated dosage of the study drug, 10 milligrams twice a day in younger patients and three times a day in adults. Compliance was monitored by patient guardians, who filled out a dosing form on a daily basis.

The study subjects returned for evaluations at two- and four-week intervals after beginning the six-week-long treatment. The drug then was tapered down over a one- to two-week period. After a week, the subjects entered a second treatment period.

The effects of the medication were scored on variables of the Aberrant Behavior Checklist, a behavior-rating scale for the assessment of drug-treatment effects. The checklist includes variables for irritability, lethargy/withdrawal, stereotypic (repetitive) behavior and hyperactivity, among other factors.

The study found improvement for the full study population on the social-avoidance subscale, an analysis validated by secondary ratings from parent observation of improvement in subjects' three most problematic behaviors. It found that the medication was the same as placebo, however, on the subscale for irritability.


Story Source:

The above story is based on materials provided by Rush University Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. E. M. Berry-Kravis, D. Hessl, B. Rathmell, P. Zarevics, M. Cherubini, K. Walton-Bowen, Y. Mu, D. V. Nguyen, J. Gonzalez-Heydrich, P. P. Wang, R. L. Carpenter, M. F. Bear, R. J. Hagerman. Effects of STX209 (Arbaclofen) on Neurobehavioral Function in Children and Adults with Fragile X Syndrome: A Randomized, Controlled, Phase 2 Trial. Science Translational Medicine, 2012; 4 (152): 152ra127 DOI: 10.1126/scitranslmed.3004214

Cite This Page:

Rush University Medical Center. "Medication effective in treating social withdrawal in Fragile X and potentially autism patients." ScienceDaily. ScienceDaily, 19 September 2012. <www.sciencedaily.com/releases/2012/09/120919142140.htm>.
Rush University Medical Center. (2012, September 19). Medication effective in treating social withdrawal in Fragile X and potentially autism patients. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2012/09/120919142140.htm
Rush University Medical Center. "Medication effective in treating social withdrawal in Fragile X and potentially autism patients." ScienceDaily. www.sciencedaily.com/releases/2012/09/120919142140.htm (accessed July 31, 2014).

Share This




More Mind & Brain News

Thursday, July 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Dieting At A Young Age Might Lead To Harmful Health Habits

Dieting At A Young Age Might Lead To Harmful Health Habits

Newsy (July 30, 2014) Researchers say women who diet at a young age are at greater risk of developing harmful health habits, including eating disorders and alcohol abuse. Video provided by Newsy
Powered by NewsLook.com
It's Not Just Facebook: OKCupid Experiments With Users Too

It's Not Just Facebook: OKCupid Experiments With Users Too

Newsy (July 29, 2014) If you've been looking for love online, there's a chance somebody has been looking at how you're looking. Video provided by Newsy
Powered by NewsLook.com
How Your Face Can Leave A Good Or Bad First Impression

How Your Face Can Leave A Good Or Bad First Impression

Newsy (July 29, 2014) Researchers have found certain facial features can make us seem more attractive or trustworthy. Video provided by Newsy
Powered by NewsLook.com
Losing Sleep Leaves You Vulnerable To 'False Memories'

Losing Sleep Leaves You Vulnerable To 'False Memories'

Newsy (July 27, 2014) A new study shows sleep deprivation can make it harder for people to remember specific details of an event. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

More Coverage


New Targeted Drug for Treating Fragile X Syndrome, Potentially Autism, Is Effective

Sep. 19, 2012 An investigational compound that targets the core symptoms of fragile X syndrome is effective for addressing the social withdrawal and challenging behaviors characteristic of the condition, making it ... read more
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



    Save/Print:
    Share:

    Free Subscriptions


    Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

    Get Social & Mobile


    Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

    Have Feedback?


    Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
    Mobile: iPhone Android Web
    Follow: Facebook Twitter Google+
    Subscribe: RSS Feeds Email Newsletters
    Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins