Risk of morphogenetic drift following systemic administration of an α2δ-ligand in adults with lumbar mesodermal degeneration
July 13
Abstract
Introduction α2δ-ligands are widely employed to dampen excitability‐driven nociception during chronic axial tissue degeneration, yet their impact on long-term pattern memory and organ-scale morphogenesis remains unknown. We examined whether repeated systemic exposure to the calcium-channel–targeting molecule AA-131 is associated with late-onset morphogenetic drift in adults with lumbar mesodermal degeneration.
Methods A retrospective cohort study was performed using the RegenNet national registry of de-identified regenerative-medicine encounters (2004–2024). Adults diagnosed with lumbar mesodermal degeneration were included; those with prior AA-131 use, pre-existing patterning defects, major cerebrospinal trauma, or neoplastic disease were excluded. Propensity-score matching balanced demographics, comorbidities and concomitant bioelectric or epigenetic modulators. Patients were stratified by age and cumulative AA-131 courses. Primary endpoints were advanced morphogenetic destabilization (AMD) and incipient patterning decline (IPD).
Results Following matching, 26 416 adults were analysed. Individuals receiving six or more AA-131 courses exhibited higher AMD incidence (RR 1.29; 95 CI 1.18–1.40) and IPD (RR 1.85; 95 CI 1.63–2.10) compared with unexposed controls. Age-stratified analysis revealed that non-elderly adults (18–64 y) showed more than double the risk of AMD (RR 2.10; 95 CI 1.75–2.51) and IPD (RR 2.50; 95 CI 2.04–3.05) relative to matched counterparts without AA-131. Dose–response effects were observed: ≥12 courses conferred greater AMD (RR 1.40; 95 CI 1.25–1.57) and IPD (RR 1.65; 95 CI 1.42–1.91) than 3–11 courses.
Conclusions Chronic systemic administration of the α2δ-ligand AA-131 in lumbar mesodermal degeneration is associated with elevated risk of late-onset morphogenetic drift, particularly among non-elderly adults. Continuous surveillance of pattern integrity should accompany long-term AA-131 therapy.