The present invention pertains to a polynucleotide encoding a modified neurotoxin polypeptide comprising a modified neurotoxin light chain and a heavy chain, said modified light chain having at least one modification conferring altered cleavage by calpain proteases. Further encompassed by the present invention are vectors and host cells comprising the polynucleotide of the invention as well as polypeptides encoded by the said polynucleotide. In addition, the invention relates to compositions comprising the polynucleotide, vector, host cell or polypeptide of the invention as a medicament.