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: Exploratory Study of NS-065/NCNP-01 in DMD

Eligibility criteria:
Inclusion Criteria:

        Subject with Duchenne muscular dystrophy eligible for enrolment in the study must meet all
        of the following criteria:

          1. Has an out of frame deletion(s) that could be corrected by skipping exon 53 as
             confirmed by any of methodology at the time of visit 1. If not confirmed by any of
             methodology that evaluates the relative copy number of all exons (i.e. MLPA, CGH etc),
             must be confirmed through these techniques by the time of visit 4.

          2. DNA sequencing of exon 53 confirms that no DNA polymorphisms occur that could
             compromise duplex formation between NS-065/NCNP-01 and pre-mRNA.

          3. There is confirmation of detection of dystrophin mRNA with skipping of exon 53 and
             dystrophin production after in vitro exposure of NS-065/NCNP-01 to subject-derived
             cells.

          4. Male and >= 5 years and < 18 years of age at the time of obtaining informed consent
             and/or assent.

          5. Able to give informed consent in writing signed by parent(s) or legal guardian who is
             able to understand all of the study procedure requirements. If applicable, able to
             give informed assent in writing signed by the subject.

          6. Life expectancy of at least 1 year

          7. Unable to ambulate. Ambulant subject can be enrolled according to the circumstances.

          8. Have intact muscles, which have adequate quality for biopsy. (No lacks or severe
             atrophy of tibialis anterior muscle)

          9. QTc <450 msec (based on 12-lead ECGs), or <480 msec for subject with Bundle Branch
             Block.

         10. If taking glucocorticosteroids, no significant change in total daily dosage or dosing
             regimen after the time of visit 1.

        Exclusion Criteria:

        Subject with Duchenne muscular dystrophy meeting any of the following criteria must not be
        enrolled in the study:

          1. Has participated in other pharmacological clinical trial that might recover dystrophin
             protein by the readthrough or the exon-skipping therapy, and/or upregulate the
             dystrophin-associated proteins such as utrophin.

          2. A forced vital capacity (FVC) < 50% of predicted.

          3. A left ventricular ejection fraction (EF) < 40% or fractional shortening (FS) < 25%
             based on echocardiogram (ECHO).

          4. Surgery within the last 3 months prior to the first anticipated administration of
             study medication or planned for anytime during the duration of the study.

          5. Positive hepatitis B surface antigen (HbsAg), hepatitis C antibody test (HCV), or
             human immunodeficiency virus (HIV) test at screening.

          6. Current diagnosis of any immune deficiency or autoimmune disease.

          7. Current diagnosis of any active or uncontrolled infection, cardiomyopathy, or liver or
             renal disease.

          8. Use of any other investigational agents and/or experimental agents within 3 months
             prior to the first anticipated administration of study medication.

          9. History of any severe drug allergy.

         10. Unable to give informed consent about using adequate contraception from the first
             administration until at least 6 months after the last dose of study medication, by
             parent(s) or legal guardian.

         11. Subject considered by the investigator (or sub-investigator), for any reason, to be an
             unsuitable candidate 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