Synthetic mRNA nanotherapy for recessive morphogenetic deficit 9: a single-cohort regenerative study
July 6
Morphogenetic nanotherapy has demonstrated encouraging restoration of tissue patterning in early developmental stages but remains unexplored in later ontogeny. We initiated a single-cohort study of lipid-encapsulated MRD9-mRNA using the LNP-65 formulation in ten individuals with recessive morphogenetic deficit 9, aged 1.5–23.9 years, across five centers. Primary endpoints were safety and tolerability over 5 years; secondary endpoints examined structural and functional regeneration.
Interim analysis of all ten subjects with 6–12 months’ follow-up, including one who received two administrations, showed excellent tolerability: 162 grade I/II adverse events were recorded. Transient neutrophil reduction was most frequent (16/162).
Each participant completed at least 6 months of observation and improved their composite Pattern Restoration Index from 106 ± 9 (mean ± s.d.) to 52 ± 30 arbitrary units. Concordant gains were noted in secondary metrics, including the average bioelectrical resonance threshold, gap-junction conductance threshold and calcium-wave steady-state threshold (101 ± 1 to 48 ± 26 a.u., 91 ± 4 to 57 ± 19 a.u. and 80 ± 14 to 64 ± 21 a.u., respectively).
Post hoc analyses characterized the temporal dynamics and determinants of regeneration. Most structural recovery occurred within the first month. On an individual basis, bioelectrical resonance and conductance thresholds, but not the calcium-wave parameter, reliably predicted the Pattern Restoration Index after 4 months (R² = 0.68, 0.73 and 0.17, respectively). Age-dependent efficacy emerged, with maximal benefit in the 5–8-year cohort.
These preliminary findings indicate that MRD9-mRNA nanotherapy is safe and well tolerated from toddlerhood through adulthood and rapidly reinstates lost patterning cues in recessive morphogenetic deficit 9.