Treatment methods using atoxic neurotoxin derivatives

A treatment method comprising:

• selecting a subject in need of therapeutic treatment involving induction of muscle paralysis and
• contacting the subject with an isolated, physiologically active derivative of a wild type Clostridium botulinum neurotoxin, wherein the derivative of a Clostridium botulinum neurotoxin comprises one or more amino acid substitutions relative to the wild type Clostridium botulinum neurotoxin that reduces the metalloprotease activity responsible for the toxicity of wild type Clostridium botulinum neurotoxin and wherein the neurotoxin derivative comprises:
• a light chain region and
• a heavy chain region, wherein the light and heavy chain regions are linked by a disulfide bond, and wherein the light and heavy chain regions are not truncated,
• said contacting being carried out to induce muscle paralysis in the subject to treat the subject, with the proviso that the neurotoxin derivative does not possess a cargo attachment peptide sequence at its N-terminus.