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Interagency Autism Coordinating Committee (IACC)
Autism Research Database
Office of Autism Research Coordination (OARC)
 
Project Element Element Description

Project Title

Project Title

MEG/MRS Dose Response Study of STX209 in ASD

Principal Investigator

Principal Investigator

Roberts, Tim

Description

Description

Timothy Roberts and his colleagues at the Childrenís Hospital of Philadelphia are studying the responsiveness of neural oscillatory measures to acute administration of STX209 (arbaclofen), a GABA-B agonist and a candidate therapeutic for autism spectrum disorder (ASD). Previous electrophysiological magnetoencephalographic (MEG) studies have pointed to auditory encoding abnormalities (specifically, delays)1,2 as well as abnormalities in the oscillatory behavior of auditory cortex neurons (especially in the gamma band: 30-50 Hz)3 in individuals with ASD. Preliminary data suggest that a GABA-B agonist may normalize activity in auditory cortex neural circuits in ASD. In the current study, Roberts and his colleagues plan to examine the acute effects of STX209 on auditory brain activity in individuals with ASD. Three different doses of STX209 (5, 15 and 25 mg), as well as placebo, will be acutely administered as part of a 4-week randomized, crossover trial. A primary goal is to assess the responsiveness (sensitivity to change) of MEG measures to acute administration of STX209 by examining MEG brain measures before, during and after administration of STX209. The researchers also aim to establish whether such electrophysiological measures are associated with GABA and glutamate levels using MEGA-PRESS spectrally edited magnetic resonance spectroscopy (MRS). This technique has previously been used to demonstrate a relationship between GABA concentration and gamma oscillatory activity in the motor cortex4. Results from this study are expected to demonstrate the utility of MEG and MRS for assessing the acute effects of STX209 on brain activity, potentially providing a physiologically specific basis for identifying those individuals with ASD most likely to benefit from STX209 treatment (i.e., targeted treatment). References: 1. Roberts T.P. et al. Biol. Psychiatry 70, 263-269 (2011) PubMed 2. Roberts T.P. et al. Autism Res. 3, 8-18 (2010) PubMed 3. Gandal M.J. et al. Biol. Psychiatry 68, 1100-1106 (2010) PubMed 4. Gaetz W. et al. Neuroimage 55, 616-621 (2011) PubMed

Funder

Funder

Simons Foundation

Fiscal Year Funding

Fiscal Year Funding

59903

Current Award Period

Current Award Period

2015-2015

Strategic Plan Question

Strategic Plan Question

Question 1: When Should I Be Concerned?

Strategic Plan Objective

Strategic Plan Objective

Green dot: Objective has greater than or equal to the recommended funding. 1LA. Identify behavioral and biological markers that separately, or in combination, accurately identify, before age 2, one or more subtypes of children at risk for developing ASD, and evaluate whether these risk markers or profiles can improve early identification through heightened developmental monitoring and screening by 2014. IACC Recommended Budget: $33,300,000 over 5 years.

Project Link

Project Link

MEG/MRS Dose Response Study of STX209 in ASD (External web link)

Institution

Institution

Children's Hospital of Philadelphia

State/Country

State/Country

Pennsylvania

Project Number

Project Number

276932

Federal or Private?

Federal or Private?

Private

Received ARRA Funding?

Received ARRA Funding?

No

History/Related Projects

History/Related Projects

N/A

 
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