MATERIALS AND METHODS FOR TREATMENT OF SPINAL MUSCULAR ATROPHY AND TAXANE-INDUCED PERIPHERAL NEUROPATHY (TIPN)

摘要

The present invention concerns materials and methods for treating, inhibiting the progression or, and/or preventing a disorder associated with and/or characterized by neuronal degeneration, such as SMA or TIPN, in a person or animal. One aspect of the invention pertains to a fusion protein comprising: i) an SMN polypeptide portion, or a fragment or variant thereof having SMN biological activity, and ii) a non-toxic BoTN portion, or a fragment or variant thereof capable of providing for receptor-mediated endocytosis in a cell, such as a neuron. In one embodiment, the SMN protein is a human SMN1 protein. In one embodiment, the BoTN portion comprises the BoTN heavy chain, or a fragment or variant thereof capable of providing for receptor-mediated endocytosis in a cell. The non-toxic BoTN portion can optionally comprise a modified and/or hybrid polypeptide that comprises amino acid sequences or polypeptides from non-BoTN proteins or polypeptides and optionally BoTN polypeptides. For example, in one embodiment, a non-toxic BoTN portion of the invention comprises a non-toxic portion of a diphtheria toxin and/or tetanus toxin.