Gene Transfer Clinical Trial for Mucopolysaccharidosis (MPS) IIIB

Adeno-associated virus serotype 9 carrying the human NAGLU gene under the control of a CMV
enhancer/promoter (rAAV9.CMV.hNAGLU) will be delivered one-time through a venous catheter
inserted into a peripheral limb vein. The vector will be delivered undiluted over 10 to 20
minutes, under light to moderate sedation as needed. Dosing volume will be approximately 2-5
mL/kg, depending on final vector product concentration and subject cohort. A tapering course
of prophylactic enteral prednisolone will be administered.

Inclusion Criteria:

- Age 6 months old or greater

- Confirmed diagnosis of MPSIIIB by both of the following two methods:

- No detectable or significantly reduced NAGLU enzyme activity by plasma, serum, or
leukocyte assay.

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

- Clinical history or examination features of neurologic dysfunction

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 NAGLU gene,
as judged by the principal investigator

- Has evidence of an attenuated phenotype of MPS IIIB, as judged by the principal
investigator

- Prior treatment with NAGLU enzyme replacement therapy (ERT)

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

- Inability to be safely sedated in the opinion of the clinical anesthesiologist

- 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

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

- 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, due to the requirement for multiple MRI examinations as
part of the study protocol. Subjects who are stable on anticonvulsive medications may
be included

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

- Any other situation that would exclude 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 IlIB 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 Beta-hCG result
at screening assessment (if applicable).