MEG Study of STX209

Recent evidence from magnetoencephalographic (MEG) studies in ASD have pointed to
abnormalities (specifically, delays) in auditory evoked neuromagnetic responses (e.g. M100 -
see Roberts et al., 2010, and mismatch field, MMF - see Roberts et al., 2011) as well as
abnormalities in the oscillatory behavior of auditory cortex, especially in the gamma band
(30-50Hz), at rest and in response to simple auditory stimuli (see Gandal et al., 2010 and
Cornew et al., 2012; Edgar et al., 2013). The local circuitry underlying such evoked activity
and oscillations, and synaptic transmission in general, requires an appropriate balance of
excitation and inhibition, mediated by glutamate and GABA, respectively. One model of the
neural oscillatory deficits in ASD suggests that impaired regulatory control by inhibitory
interneurons onto pyramidal cells underlies abnormal auditory latency and oscillatory
electrophysiological measures. As such, electrophysiological deficits are interpreted in
terms of local circuitry abnormalities, with inferences at the molecular level of imbalances
in the activity of glutamate and GABA.

A candidate therapeutic for ASD has been developed - STX209, a GABA-B agonist. Since this
pharmaceutical targets synaptic activity that has clear electrophysiological correlates, one
goal of this proposal is to assess the responsiveness (sensitivity to change) of MEG measures
to acute administration of STX209 at various doses in adolescents on the autism spectrum. The
study also aims to establish the nature of the putative relationship between such
electrophysiologic markers and GABA and glutamate levels using MEGAPRESS spectrally-edited
magnetic resonance spectroscopy (MRS).

Inclusion Criteria:

1. Right- handed males aged 14 to 17.75 years.

2. Diagnosis of ASD with the last 12 months according to the DSM-IV criteria, including
Autistic Disorder, Pervasive Developmental Disorder - Not Otherwise Specified
(PDD-NOS), and Asperger's Syndrome but excluding Childhood Dis-integrative Disorder
and Rett Syndrome.

3. Current pharmacological treatment regimen has been stable for at least 4 weeks prior
to Screening.

4. If the subject is already receiving stable non-pharmacological educational,
behavioral, and/or dietary interventions, participation in these programs must have
been continuous during the 2 months prior to Screening and subjects or their
parent/caregiver may not electively initiate new or modify ongoing interventions for
the duration of the study. Typical school vacations are not considered modifications
of stable programming.

5. Prior to the conduct of any study-specific procedures, the subject must provide verbal
assent to participate in the study (if developmentally appropriate), and the
parent/caregiver must provide written informed consent. If the caregiver attending the
clinic visits is not the parent, written consent must be obtained from the parent for
the caregiver's participation in the study.

Exclusion Criteria:

1. No known neurological impairment (e.g., head trauma with loss of consciousness for
more than 10 minutes, stroke, seizure disorder).

2. Claustrophobia

3. Metallic implanted prosthetic or stimulation device (including pacemaker)

4. Excessive metallic dental work (including braces, non-removable retainers)

5. Subjects who are currently receiving treatment with racemic baclofen, vigabatrin,
tiagabine, or riluzole.

6. Subjects who have taken another investigational drug within the last 30 days.

7. Subjects who are not able to take oral medications.

8. Subjects who have a history of hypersensitivity to racemic baclofen.

9. Parents/guardians or subjects who, in the opinion of the Investigator, may be
non-compliant with study schedules or procedures.