Intermediate outcomes of the phase I / II gene therapy trial with SRP-9003 (scAAVrh74.MHCK7.hSGCB) in children with LGMDR4 linked to β-sarcoglycan (ex-LGMD2E), aged 4 to 13 years, were announced at the annual conference of MDA, the American Muscular Dystrophies Association.
This 3-year, single-injection, intravenous infusion safety trial of SRP-9003 tested the tolerance of a first dose for one year in the first 3 participants, before administering a four-fold dose in three other participants.
The administration of SRP-9003 was accompanied by initiation of prednisone (1 mg / kg / day) the day before the infusion and for a period of one month followed by gradual discontinuation over one month.
With a follow-up of 2 years for the first cohort (low dose) and one year for the second (high dose),
- SRP-9003 did not cause serious side effects (no thrombocytopenia or signs of complement activation in particular);
- mean β-sarcoglycan expression was 36% of normal at 2 months and 54% at 2 years; at the high dose, expression of δ- and γ-sarcoglycans was near-normal in at least 60% of muscle fibers, probably indicative of a restoration of the dystrophin-associated protein complex;
- the improvement in scores on the NSAD (North Star Assessment for Dysferlinopathies) functional scale was 5.7 on average and was maintained during the two years with the low dose (while this score declined on average from 4.6 on the same period in natural history studies);
- it was 4 points on average at one year with the high dose;
- all the participants improved their performance in the timed tests (getting up from the ground, climbing 4 steps, walking 10 meters, walking 100 meters, etc.).
