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: Dose-Ranging Study of AVI-4658 to Induce Dystrophin Expression in Selected Duchenne Muscular Dystrophy (DMD) Patients

Eligibility criteria:
Inclusion Criteria:

          1. Has provided written informed assent (as required by EC) and parents/guardians have
             provided written informed consent.

          2. Has an out-of-frame deletion(s) that could be corrected by skipping exon 51 based on
             DNA sequencing data from the candidate.

          3. Is male and between the ages of ≥ 5 years and ≤ 15 years.

          4. Has a muscle biopsy analysis showing < 5% revertant fibres present at baseline.

          5. DNA sequencing of the candidate's dystrophin exon 51 confirms that no DNA
             polymorphisms are present that could compromise PMO duplex formation or there is
             confirmation of in vitro dystrophin production after AVI-4658 exposure to fibroblast
             or myoblast in vitro cultures.

          6. Intact right and left bicep muscles or alternative arm muscle group.

          7. Is able to walk independently at least 25 meters.

          8. Has a forced vital capacity (FVC) ≥ 50% of predicted and does not require ventilatory
             support or supplemental oxygen.

          9. Receives the standard of care for DMD as recommended by the DMD care recommendations
             from the North Star UK and TREAT-NMD.

         10. The parent(s) or legal guardian and Subject have undergone counselling about the
             expectations of this protocol and agree to participate.

         11. The parent(s) or legal guardian and Subject intend to comply with all study
             evaluations and return for all study activities.

        Exclusion Criteria:

          1. A DNA polymorphism within exon 51 that may compromise PMO duplex formation.

          2. Known antibodies to dystrophin.

          3. Lacks intact right and left bicep muscles or alternative arm muscle group.

          4. A calculated creatinine clearance less than 70% of predicted normal for age based on
             the Cockcroft and Gault Formula.

          5. A left ventricular ejection fraction (EF) of < 35% and/or fractional shortening of
             <25% based on echocardiography (ECHO)during screening.

          6. A history of respiratory insufficiency as defined by need for intermittent or
             continuous supplemental oxygen.

          7. A severe cognitive dysfunction rendering the potential subject unable to understand
             and comply with the study protocol.

          8. Any known immune deficiency or autoimmune disease.

          9. A known bleeding disorder or has received chronic anticoagulant treatment within three
             months of study entry.

         10. Receipt of pharmacologic treatment, apart from corticosteroids, that might affect
             muscle strength or function within 8 weeks of study entry (viz., growth hormone,
             anabolic steroids).

         11. Surgery within 3 months of study entry or planned for anytime during the duration of
             the study.

         12. Another clinically significant illness at time of study entry.

         13. Subject or parent has active psychiatric disorder, has adverse psychosocial
             circumstances,recent significant emotional loss, and/or history of depressive or
             anxiety disorder that might interfere with protocol compliance.

         14. Use of any experimental treatments, has participated in any DMD interventional
             clinical trial within 4 weeks of study entry or participated in the AVI-4658-33
             intramuscular (i.m.) trial.
Male
No healthy subjects accepted to join the trial.
Subject must be at least 5 Years old.
Subject must be at most 15 Years

Eligibility (NLI label): Entailment