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Comparative Study
. 2022 Oct 28;14(11):739.
doi: 10.3390/toxins14110739.

A Pilot Study of A2NTX, a Novel Low-Molecular-Weight Neurotoxin Derived from Subtype A2 for Post-Stroke Lower Limb Spasticity: Comparison with OnabotulinumtoxinA

Ryuji Kaji  1   2 , Ai Miyashiro  1 , Nori Sato  3 , Taiki Furumoto  3 , Toshiaki Takeuchi  1   2 , Ryosuke Miyamoto  1 , Tomoko Kohda  4 , Yuishin Izumi  1 , Shunji Kozaki  4
Affiliations
Comparative Study

A Pilot Study of A2NTX, a Novel Low-Molecular-Weight Neurotoxin Derived from Subtype A2 for Post-Stroke Lower Limb Spasticity: Comparison with OnabotulinumtoxinA

Ryuji Kaji et al. Toxins (Basel). .

Abstract

All the currently used type A botulinum neurotoxins for clinical uses are of subtype A1. We compared the efficacy and safety for the first time head-to-head between a novel botulinum toxin A2NTX prepared from subtype A2 and onabotulinumtoxinA (BOTOX) derived from A1 for post-stroke spasticity. We assessed the modified Ashworth scale (MAS) of the ankle joint, the mobility scores of Functional Independence Measure (FIM), and the grip power of the unaffected hand before and after injecting 300 units of BOTOX or A2NTX into calf muscles. The procedure was done in a blinded manner for the patient, the injecting physician, and the examiner. Stroke patients with chronic spastic hemiparesis (15 for A2NTX and 16 for BOTOX) were enrolled, and 11 for A2NTX and 13 for BOTOX (MAS of ankle; > or = 2) were entered for the MAS study. Area-under-curves of changes in MAS (primary outcome) were greater for A2NTX by day 30 (p = 0.044), and were similar by day 60. FIM was significantly improved in the A2NTX group (p = 0.005), but not in the BOTOX group by day 60. The hand grip of the unaffected limb was significantly decreased in the BOTOX-injected group (p = 0.002), but was unaffected in the A2NTX-injected group by day 60, suggesting there was less spread of A2NTX to the upper limb than there was with BOTOX. Being a small-sized pilot investigation with an imbalance in the gender of the subjects, the present study suggested superior efficacy and safety of A2NTX, and warrants a larger scale clinical trial of A2NTX to confirm these preliminary results.

Keywords: A2NTX; Functional Independence Measure; botulinum neurotoxin; clinical efficacy; hand grip; onabotulinumtoxinA; safety; spasticity: modified Ashworth scale; spread; subtype A2.

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Conflict of interest statement

A patent on A2NTX (WO 2008/050866) is owned by Tokushima University and Shionogi Pharma, Osaka, Japan.

Figures

Figure 1
Figure 1
Flow chart for patients’ disposition.
Figure 2
Figure 2
Changes of MAS. Each bar indicates the difference of MAS between day 0 and day 30, 60, and 90. Solid line on top indicates standard errors. * indicates significant difference.
Figure 3
Figure 3
Changes of MAS/AUC (~day 30/~day 60: primary outcomes). * indicates significant difference.
Figure 4
Figure 4
Functional Independence Measures (FIM) at day 30 and day 60. Each bar indicates individual subjects in different colors. A2NTX group showed highly significant improvement within group comparison at day 60 (paired-t). * indicates significant difference.
Figure 5
Figure 5
Hand Grip Power (in kg torque) of the unaffected side. Each bar indicates individual subjects in different colors. OnaA group showed significant drop of grip power at day 30 and 60 within group (paired-t). * indicates significant difference.
Figure 6
Figure 6
Method for injection.
Figure 7
Figure 7
Summary of injection and evaluation schedule.
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