Abstract: Aspects of the disclosure relate to Botulinum toxin X (BoNT X) protein variants. The variants provided herein have been evolved to cleave GTP cyclohydrolase 1 (GCH1). Some of the variants provided herein were evolved from a procaspase-1 cleaving polypeptide. Further aspects of the disclosure relate to nucleic acids encoding the GCH1 cleaving polypeptides described herein and expression vectors comprising the nucleic acids, as well as host cells and fusion proteins comprising the GCH1 cleaving polypeptides described herein, and kits comprising the GCH1 polypeptides, fusion proteins, nucleic acids, expression vectors, or host cells described herein. Further aspects of the disclosure relate to methods of producing BoNT X variants and methods of using the BoNT X protein variants, for example, to reduce pain.

Abstract: This invention relates to compositions and methods for the transplantation of GABAergic neurons. GABAergic neurons and compositions comprising the same according to the present invention may be used as cell-based therapies for restoring or reinforcing central inhibition in the nervous system of a subject and for the treatment of neurological conditions, diseases and disorders associated with impaired or aberrant neural function. In a preferred embodiment, the transplant composition comprise of GABAergic neurons, a GFR-alpha agonist, and at least one cell death inhibitor, and that the GABAergic neurons are generated by differentiating pluripotent stem cells, multipotent stem cells, or progenitor cells.