Clinical differences between A1 and A2 botulinum toxin subtypes.

All the type A botulinum toxins that have been clinically used are of subtype A1. We have developed low-molecular weight (150 k Dal) subtype A2 preparation (A2NTX) for clinical use. In the first-in-man study, the clinical efficacy of A2NTX was 1.5 times that of onabotulinumtoxinA (subtype A1) with similar time course and less spread of its action to a neighboring muscle. We have recently performed a comparative study of A1LL (onabotulinumtoxinA) and A2NTX toxins for post-stroke spasticity (Study of a New Generation Botulinum Toxin A2NTX to Treat Spasticity After Stroke; NCT01910363 at ClinicalTrials.gov). This double blinded randomized controlled study used 300u of each subtype. In this study, A2NTX showed significantly higher efficacy 30 days after injection (Fig. 2), and less spread of the effect as measured by the hand grip of the unaffected side than A1LL. Functional independence measure (FIM) was also significantly improved for A2NTX, but not for A1LL. Additional large-scale clinical trials are warranted to further evaluate this promising new treatment.