Healthy Volunteers Clinical Trial
Official title:
Neuroimmune Activation in Austism: Imaging Translocator Protein Using Positron Emission Tomography (PET)
Background:
- People with autism and autism spectrum disorders have problems with communication,
behavior, and socializing, and many also have intellectual and developmental disabilities.
The cause of autism is not known, but previous research has suggested an association between
autism and immune changes in the brain. Researchers are interested in using the experimental
radioactive drug (11C)PBR28, which attaches to a protein in the brain that is involved in
immune changes, in positron emission tomography (PET) scanning of people with and without
autism to see if there are greater immune changes in those with autism.
Objectives:
- To determine if positron emission tomography scanning can be used to evaluate changes in an
immune system protein in the brains of people with autism.
Eligibility:
- Individuals between 18 and 45 years of age who have been diagnosed with either autism or
autism spectrum disorders, or are healthy volunteers.
Design:
- Participants will be screened with a physical examination and psychological examination,
medical history, questionnaires about behavior and mood, and blood and urine tests.
- Participants will have two imaging studies of the brain at separate study visits. The
first study visit will involve a magnetic resonance imaging (MRI) scan to provide a
baseline image of the brain. The second study visit will involve PET scan with the
radioactive chemical (11C)PBR28 to study immune system proteins in the brain. The MRI
scan will take about 40 minutes, and the PET scan will take about 2 hours.
- Participants will have a final study visit 24 hours after the PET scan to provide a
final blood sample for testing.
Current estimates indicate that 1 in 110 children are affected with autism. Despite this
striking statistic, we remain unable to describe the pathophysiology for autism, and we do
not have adequate treatments for autism. The etiologies in most patients with autism are
unknown, but emerging evidence supports a causal role of immune activation in autism.
Multiple studies provide clear evidence of immune activation in peripheral blood of patients
with autism, as demonstrated by elevations in immune markers (IFN-gamma, IL-1RA, IL-6, and
TNF-alpha). Studies also demonstrate immune activation in cerebrospinal fluid (CSF) of
patients with autism, as evidenced by significant elevations in cytokines and TNF-alpha.
Finally, three postmortem brain studies report neuroimmune activation in patients with autism
(ages 4-45). Combined, these three postmortem studies show activation of microglia and
astroglia through elevations in cytokines, histology and stereology.
While the growing body of literature supporting neuroimmune activation in autism is
intriguing, the current results present limitations. First, there are no studies assessing
the brains of living patients with autism/ASDs. Second, the most convincing evidence for
neuroimmune activation in postmortem brains is extracted almost exclusively from patients
with classical autism, where intellectual disability is common. As such, the evidence for
neuroimmune activation in higher functioning patients with autism and autism spectrum
disorders (ASDs) is less robust.
We propose to determine whether neuroimmune activation is present in the living brains of
patients with autism. Furthermore, given the heterogeneity of the autisms , as they are now
called, we would like to determine whether neuroimmune activation is detectable in higher
versus lower functioning patients with autism/ASDs. We propose to measure neuroimmune
activation in the living brains of patients by utilizing positron emission tomography (PET)
and the radioligand [(11)C]PBR28. This radioligand binds translocator protein (TSPO), which
is over-expressed in activated microglia and reactive astrocytes, and has been demonstrated
as a reliable marker of neuroimmune activation in various neuropsychiatric disorders. Because
the majority of patients with autism/ASD will require propofol sedation to remain motionless
for the two hour scan, we will include a control arm with healthy volunteers without then
with propofol in order to determine the effects of propofol on [(11)C]PBR28 uptake. NIH has
developed a setup in the clinical center for administering sedation/anesthesia in a safe
manner, making this important study possible.
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