Systemic Gene Delivery Clinical Trial for Duchenne Muscular Dystrophy

In the study, the gene will be infused via peripheral arm vein so that it can reach all the
muscles in the body. Six DMD subjects ages 3 months to 3 years in Cohort A, and six DMD
subjects ages 4 years to age 7 years in Cohort B, will be enrolled. All subjects will receive
intravenous micro-dystrophin vector (2X10e14 vg/kg in 10mL/kg). Subjects will have infusions
over 1 hour in the Pediatric Intensive Care Unit (PICU) at Nationwide Children's Hospital.
Before the gene therapy a muscle biopsy will be done at the screening visit. Subjects will
have a second muscle biopsy to see if the gene allowed for replacement of the missing
dystrophin protein at 90 days post delivery. After the gene transfer, patients will be
carefully monitored for any side effects of the treatment. This will include blood and urine
tests, as well as physical examination during the screening visits and on days 0, 1, 7, 14,
30, 60, 90, and 180, and at months 9, 12, 18, 24, 30 and 36 to make sure that there are no
side effects from the gene injection.

Inclusion Criteria:

- Cohort A subjects: 3 months to 3 years of age, inclusive

- Cohort B subjects: 4 to 7 years of age, inclusive

- Molecular characterization of the DMD gene with frameshift (deletion or duplication),
or premature stop codon mutation between exons 18 to 58

- CK elevation >1000 U/L

- Cohort A subjects: below average on the Bayley-III motor assessment for gross motor
defined as a scaled score of ≤9.

- Cohort B subjects: below average on the 100 Meter Timed Test defined as ≤ 80%
predicted.

- Males of any ethnic group

- Ability to cooperate with motor assessment testing.

- Cohort A subjects: No previous treatment with corticosteroids.

- Cohort B subjects: Stable dose equivalent of oral corticosteroids for at least 12
weeks prior to screening and the dose is expected to remain constant (except for
modifications to accommodate changes in weight) throughout the study.

Exclusion Criteria:

- Active viral infection based on clinical observations.

- Signs of cardiomyopathy, including echocardiogram with ejection fraction below 40%.

- Serological evidence of HIV infection, or Hepatitis B or C infection.

- Diagnosis of (or ongoing treatment for) an autoimmune disease.

- Abnormal laboratory values considered clinically significant.

- Concomitant illness or requirement for chronic drug treatment that in the opinion of
the PI creates unnecessary risks for gene transfer.

- Subjects with AAVrh74 or AAV8 antibody titers > 1:400 as determined by ELISA
immunoassay.

- Medical condition or extenuating circumstance that, in the opinion of the
investigator, might compromise the subject's ability to comply with the protocol
required testing or procedures or compromise the subject's wellbeing, safety, or
clinical interpretability.

- Severe infection (e.g., pneumonia, pyelonephritis, or meningitis) within 4 weeks
before gene transfer visit (enrollment may be postponed).

- Received any investigational medication (other than corticosteroids) or exon skipping
medications (including ExonDys 51), experimental or otherwise, in the last 6 months
prior to screening for this study.

- Received any type of gene therapy, cell based therapy (e.g. stem cell
transplantation), or CRISPR/Cas9.

- Family does not want to disclose patient's study participation with primary care
physician and other medical providers.