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: A Phase I/II Study of BMN053 in Subjects With Duchenne Muscular Dystrophy (DMD)

Eligibility criteria:
Inclusion Criteria:

          1. Duchenne muscular dystrophy resulting from a mutation correctable by treatment with
             BMN053 confirmed by a state-of-the-art DNA diagnostic technique covering all DMD gene
             exons, including but not limited to MLPA (Multiplex Ligation-dependent Probe
             Amplification), CGH (Comparative Genomic Hybridisation), SCAIP (Single Condition
             Amplification/Internal Primer) or HRMCA (High-Resolution Melting Curve Analysis).

          2. Ambulant boys aged at least 5 years on the day of first dosing able to walk for at
             least 300 metres in the 6 minute walking distance (6MWD) test. In addition, results of
             the 6MWD test must be within ±30 metres of each other at 2 of 3 pre-treatment visits
             (screen 1, 2 and baseline) prior to first BMN053 administration.

          3. Adequate quality for biopsy (confirmed with MRI) of the lateral head of the
             gastrocnemius muscle. Only under exceptional circumstances will an alternative muscle
             (preferably brachii) be considered for biopsy and only following discussion between
             the Principal Investigator and the BioMarin Medical Monitor.

          4. Life expectancy of at least 3 years after inclusion in the study.

          5. Glucocorticosteroid use which is stable for at least 3 months prior to first BMN053
             administration. Subjects must have been receiving glucocorticosteroids for at least 6
             months prior to the first BMN053 administration.

          6. Willing and able to adhere to the study visit schedule and other protocol
             requirements.

          7. Written informed consent signed (by parent(s)/legal guardian and/or the subject,
             according to the local regulations).

          8. In France, a subject will be eligible for inclusion in this study only if either
             affiliated to, or a beneficiary of, a social security category.

          9. Anticipated adequate vein access for intravenous (IV) infusion.

        Exclusion Criteria:

          1. Current or history of liver disease or impairment.

          2. Current or history of renal disease or impairment.

          3. At least two aPTT above upper limit of normal (ULN) within the last month prior to
             first dose of BMN053.

          4. Screening platelet count below the lower limit of normal (LLN).

          5. Acute illness within 4 weeks prior to first dose of BMN053 which may interfere with
             the study assessments.

          6. Severe mental retardation and/or behavioural problems which, in the opinion of the
             Investigator, prohibit participation in this study.

          7. Severe cardiomyopathy which, in the opinion of the Investigator prohibits
             participation in this study. If a subject has a left ventricular ejection fraction
             <45% at screening, the Investigator should discuss inclusion of the subject with the
             Medical Monitor.

          8. Expected need for daytime mechanical ventilation within the next year.

          9. Use of anticoagulants, antithrombotics or antiplatelet agents.

         10. Use of idebenone or other forms of coenzyme Q10 within 1 month prior to the start of
             the screening for the study.

         11. Use of nutritional or herbal supplements which, in the opinion of the Investigator,
             may influence muscle performance within 1 month prior to first dose of BMN053.

         12. Use of any other investigational product or participation in another trial with an
             investigational product, within 6 months prior to the start of the screening for the
             study.
Male
No healthy subjects accepted to join the trial.
Subject must be at least 5 Years old.
Subject must be at most 18 Years

Eligibility (NLI label): Entailment