Patient case (clinical description): An 8-year-old boy is brought to the clinic by his parents because of weakness and difficulty of standing up from a sitting position. The mother is healthy but had a brother who died in his 20th after being disabled and using wheelchairs in the last few years of his life. Physical examination shows 3/5 lower extremity muscle strength and enlarged calf muscles. The other physical examination and vital signs are unremarkable. Muscle biopsy showed absence of dystrophin protein. The patient is diagnosed with DMD.

Patient's own account: I brought my  8-year-old son to the doctor's clinic. He was struggling to stand up from a chair for the past few days. My wife is healthy but she was pretty worried since his brother died in his 20s after being disabled and using a wheelchair for the last years of his life. The doctor did an exam which highlighted weakness in the leg muscles and unusually large calf muscles. The rest of the exam was fine, and his vitals were normal. My son did a muscle biopsy, and it showed that the protein important for muscle strength and function is missing. The doctor diagnosed him with Duchenne muscular dystrophy.

Clinical trial: Systemic Gene Delivery Clinical Trial for Duchenne Muscular Dystrophy (DMD)

Eligibility criteria:
Inclusion Criteria:

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

          -  Cohort B patients: 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 and

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

          -  Cohort B patients: 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 patients: No previous treatment with corticosteroids.

          -  Cohort B patients: 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 first year of 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.

          -  Patients with rAAVrh74 or AAV8 antibody titers > 1:400 as determined by enzyme-linked
             immunosorbent assay (ELISA) immunoassay.

          -  Medical condition or extenuating circumstance that, in the opinion of the
             investigator, might compromise the patient's ability to comply with the protocol
             required testing or procedures or compromise the patient'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.
Male
No healthy subjects accepted to join the trial.
Subject must be at least 3 Months old.
Subject must be at most 7 Years

Eligibility (NLI label): Contradiction