Gene Therapy for Purkinje Cell Disorders of the Dog and Cat

Presentation Description / Summary: Cats with NPC1 disease have a spontaneously-occurring missense mutation in NPC1 (2864G-C) and clinical, neuropathological and biochemical abnormalities similar to those present in juvenile-onset patients making this model homologous to the most common form seen in human patients. Our hypothesis is that gene therapy can be optimized to deliver a therapeutic transgene to over 75% of affected Purkinje cells. To test our hypothesis, cats with Niemann-Pick type C disease, raised in an animal colony, received an adeno-associated viral vector containing wild type NPC1 cDNA via four delivery methods. The method of administration to each cat was randomized however the investigator was not blinded to the method used. Using the optimized method of delivery, ataxia was prevented in treated cats. Using immunofluorescence, wild type NPC1 expression was identified in >50% of Purkinje cells. Our continuing work focuses on optimizing administration to result in expression in greater than 75% of Purkinje cells. This optimized method can then be used to treat Purkinje cell diseases in a number of neurodegenerative disorders.