The present invention relates to methods to treat a neurodegenerative disease or disorder, e.g., a motor neuron disease in a subject, whereby the subject is administered a recombinant human Mullerian Inhibiting Substance (MIS) protein as disclosed herein, wherein the recombinant human MIS protein comprises a modified Kex cleavage site for increased cleavage. The recombinant human MIS protein can be produced from a pre-proprotein comprising a non-MIS leader sequence or a functional fragment thereof in place of the MIS leader sequence.