Phase I/II Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH

Self-complementary adeno-associated virus serotype 9 carrying the human SGSH gene under the
control of a U1a promoter (scAAV9.U1a.hSGSH) will be delivered one time through a venous
catheter inserted into a peripheral limb vein. The vector will be delivered undiluted over 15
to 45 minutes, under sedation as needed. Dosing volume will be approximately 0.5 to 3 mL/kg,
depending on final vector product concentration and subject cohort. A tapering course of
prophylactic enteral prednisone or prednisolone will be administered

Inclusion Criteria:

- Age 6 months to 2 years or children older than 2 years with a minimum cognitive
Developmental Quotient (DQ) of 60 or above (calculated by Bayley Scales of Infant and
Toddler Development - Third Edition)

- Confirmed diagnosis of MPS IIIA by the following methods:

- No detectable or significantly reduced* SGSH enzyme activity by leukocyte assay

- Genomic DNA analysis demonstrating homozygous or compound heterozygous mutations in
the SGSH gene

Exclusion Criteria:

- Inability to participate in the clinical evaluation as determined by PI

- Identification of two nonsense or null variants on genetic testing of the SGSH gene

- At least one S298P mutation in the SGSH gene

- Has evidence of an attenuated phenotype of MPS IIIA

- Presence of a concomitant medical condition that precludes lumbar puncture or use of
anesthetics

- Active viral infection based on clinical observations

- Concomitant illness or requirement for chronic drug treatment that in the opinion of
the PI creates unnecessary risks for gene transfer or precludes the child from
participating in the protocol assessments and follow up

- Subjects with total anti-AAV9 antibody titers ≥ 1:100 as determined by ELISA binding
immunoassay

- Subjects with a positive response for the ELISPOT for T-cell responses to AAV9

- Serology consistent with exposure to HIV, or serology consistent with active hepatitis
B or C infection

- Bleeding disorder or any other medical condition or circumstance in which a lumbar
puncture (for collection of CSF) is contraindicated according to local institutional
policy

- Visual or hearing impairment sufficient to preclude cooperation with
neurodevelopmental testing

- Uncontrolled seizure disorder

- Any item (braces, etc.) which would exclude the patient from being able to undergo MRI
according to local institutional policy

- Any other situation that precludes the subject from undergoing any other procedure
required in this study

- Subjects with cardiomyopathy or significant congenital heart abnormalities

- The presence of significant non-MPS IlIA related CNS impairment or behavioral
disturbances that would confound the scientific rigor or interpretation of results of
the study

- Abnormal laboratory values Grade 2 or higher as defined in CTCAE v4.0 for GGT, total
bilirubin, creatinine, hemoglobin, WBC count, platelet count, PT and aPTT

- Female participant who is pregnant or demonstrates a positive urine or bhCG result at
screening assessment (if applicable)

- Any vaccination with viral attenuated vaccines less than 30 days prior to the
scheduled date of treatment (and use of prednisolone)

- Previous treatment by Haematopoietic Stem Cell transplantation

- Previous participation in a gene/cell therapy or ERT clinical trial

- Due to the nature of enzyme activity testing, normal ranges and reported units
vary from lab to lab. Many laboratories utilize control samples rather than
normal ranges, to account for the influence of small day-to-day fluctuations in
the laboratory environment.

- For the purposes of invitation to a screening visit, we will accept
"significantly reduced" results as those interpreted as such by any clinical
laboratory approved to perform this diagnostic test.

For uniformity of data for analysis, and confirmation of accurate diagnosis before gene
transfer, subjects who consent to complete the screening visit will have their blood drawn
for confirmatory enzyme activity level to be performed by Greenwood Genetics Center
Biochemical Laboratory. Subjects must have an enzyme activity level considered to be in the
affected range by Greenwood Genetic Center Biochemical Laboratory to proceed within the
study.