A2NTX is a unique botulinum type A neurotoxin preparation of 150 kDa derived from a subtype A2 strain of Clostridium botulinum , which solely produces M toxin of 300 kDa (No. PCNT115-3, 9.30×104 U/mL). We have shown in animal studies that A2NTX is less diffusible than BOTOX ® or Xeomin ® , and, as a consequence, with a larger safety margin as defined by the range between LD50 and ED50 (standard dose required to reduce CMAP at injection by half). To test its promise of clinical utility for treating larger muscles with hyperactivity, we conducted a pilot study to assess the safety and efficacy of this preparation in 30 patients (19 males, age 20–72 years) with lower limb spasticity ( n =15) or generalized/axial/hemi-dystonia. Selection criteria were those who failed to respond to 3 successive dosings of 300 U BOTOX over 6 months as measured by modified Rankin scale. The dosing started at least 4 months after the previous BOTOX injection. The efficacies were measured by modified Rankin scale. At Aug.1, 2007, 100–1500 U of NTX injections were made at a time, and the mean cumulative dose per subject mounted to 2954.5 U (range 100–7750 U) with no evidence of secondary unresponsiveness. After the initial 3 injections, Modified Rankin scale improved by 1 in 5 patients and by 2 in 1 patient. At present, the scale improved by 1 in 9 subjects and by 2 in 2 patients. Adverse effects included mild decrease in grasp power ( n =6) and swallowing difficulty.