Outline of the single-patient clinical trial. The schematic depicts the postdosing safety and efficacy monitoring time points, along with the immunosuppression protocol. The comprehensive immunosuppression program was implemented to attempt to minimize the innate and adaptive immune responses and to promote tolerance to the gene therapy product. GT indicates the gene therapy dosing. MRI of the brain and spine (with and without contrast) was done at baseline and at 3, 6 and 12 months after dosing. CSF analysis included cell count, protein concentration, oligoclonal bands and cytokine analysis. Exploratory tests included measurement of the AAV9 neutralizing antibody titer, serum cytokine analysis and ELISpot assay. Safety laboratory tests (safety labs) included complete blood count with differential, erythrocyte sedimentation rate, C-reactive protein, liver function tests (alanine aminotransferase, aspartate aminotransferase, -glutamyl transferase, alkaline phosphatase), blood urea nitrogen/creatinine, urinalysis, electrocardiography and cardiac safety panel (troponin, pro-B-type natriuretic peptide, creatine kinase isotype MB). IV MethylPred, intravenous methylprednisolone.
