Autism spectrum disorders (ASD) are highly disabling, persistent neurodevelopmental disorders. There are no available treatments for core symptoms of ASD or biologically-based clinical biomarkers. Emerging evidence indicates that levels of brain inflammation are increased in ASD. In particular, recent work implicates hyperactivity of microglial cells, the resident immune cells of the brain. However, the functional consequences of microglial activation remain unknown. This study will measure microglial activation in ASD using positron emission tomography (PET) brain imaging. Adult males with ASD (n=15) and healthy controls (n=15) will be recruited for this study and undergo comprehensive clinical and behavioral baseline assessment. All subjects will then undergo baseline PET imaging using a radiotracer that labels activated microglia. Subjects with ASD will then undergo 12-week open label treatment with minocycline, an FDA-approved antibiotic thought to block microglial activation. PET imaging will be repeated at 12 weeks to confirm target engagement. A subset of control subjects will also undergo repeat PET imaging to determine test-retest reliability. During minocycline treatment, ASD subjects will be evaluated every 2 weeks for safety, clinical impression, behavioral functioning, and measures of cognition. Results will provide important information regarding the relationship between levels of brain inflammation, cognitive and behavioral function in ASD.
Name: MinocyclineDescription: Following initial baseline PET-CT imaging and clinical evaluation, adults with ASD will undergo a 12- week open-label treatment trial of minocycline to be conducted at UCLA under supervision of the UCLA IRB. During weeks 1-6, ASD subjects will be treated with 50 mg minocycline twice daily (low dose). From weeks 7-12, dosing will be increased to 100mg twice daily (typical clinical dosage). Every two weeks during this phase, a treating clinician will measure vital signs, assess safety, record adverse effects, and monitor compliance. Compliance will be obtained as an index of tolerability and will assessed through weekly medication diaries and pill counts.Type: Drug
Single Group Assignment
There is one SNP
hepatic, neurologic, renal disease) to increase risk to the subject 3. Presence of severe behavioral disturbance likely to require initiation of treatment during the course of the protocol 4. Clinical judgment of the study physician of inability to perform the requirements of the study 5. Current or recent (past 30 days) treatment with minocycline or related compounds, immunosuppressives, or benzodiazepines 6. Homozygous genotype for minor allele of rs6971 7. History of recent febrile illness in past 30 days 8. History of allergic reactions to tetracycline antibiotics 9. Concomitant medication treatment not stable for the 4 weeks prior to study entry or anticipated to change 10.
hepatic, neurologic, renal disease) to increase risk to the subject 4. Presence of current or lifetime severe psychopathology potentially confounding assessment of TSPO binding (psychosis, severe depression, bipolar disorder, Obsessive-Compulsive Disorder) 5. Current prescribed medication likely to confound assessment of TSPO binding 6. Clinical judgment of the study physician of inability to perform the requirements of the study 7. Current or recent (past 30 days) treatment with minocycline or related compounds, immunosuppressives, benzodiazepines, or psychotropic medications likely to confound assessment of TSPO binding 8. Homozygous genotype for minor allele of rs6971 9. SRS-2 T-score score of >59 10.