Gene Transfer Clinical Trial for LGMD2E (Beta-sarcoglycan Deficiency) Using scAAVrh74.MHCK7.hSGCB

The proposed clinical trial is the first-in-human, randomized, double-blinded, single dose
study of self-complementary AAVrh.74 carrying the human β-sarcoglycan gene under the control
of an MHCK7 promoter (scAAVrh74.MHCK7.hSGCB) delivered through a single systemic injection in
a peripheral vein of LGMD2E patients. A minimum of nine patients will be enrolled. Cohort 1
will consist of 3 treated subjects. Based on data from Cohort 1, there is the potential to
escalate dose for Cohort 2 which will include 6 subjects randomized resulting in 3 treated
and 3 placebo subjects. Placebo subjects will be treated by completion of study.

INCLUSION CRITERIA

- Subjects ages 4 through age 15, inclusive

- Males or females of any ethnic group

- SGCB DNA gene mutations at both alleles.

- Weakness demonstrated based on history of difficulty running, jumping and climbing
stairs.

- 100m timed test: ≥40% of predicted for age, height and weight matched healthy controls
at the screening visit.

- Ability to cooperate with muscle testing.

- Willingness of sexually active subjects with reproductive capacity to practice
reliable method of contraception (if appropriate), during the first six months after
gene therapy.

EXCLUSION CRITERIA

Individuals who meet the following exclusion criteria will not be eligible to participate
in the study:

- Active viral infection based on clinical observations.

- Cardiac MRI determined ejection fraction <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 (GGT > 3XULN, bilirubin ≥
3.0 mg/dL, creatinine ≥ 1.8 mg/dL, Hgb < 8 or > 18 g/Dl; WBC > 15,000 per cmm).

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

- Pregnancy

- Subjects with AAVrh74 binding antibody titers > 1:400 as determined by ELISA
immunoassay. If endpoint titer is positive at screening, testing may be repeated in 1
month.

- Has a medical condition or circumstance that could compromise the protocol compliance
or compromise safety

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

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