AAV2/8-mediated expression of modified sulphamidase, liver targeting for improved secretion and brain delivery in IIIA Huntaway dog.

This is a pre-clinical trial of a new gene therapy approach for Sanfilippo syndrome type A. The therapy treats brain disease in mice with Sanfilippo type A (MPS IIIA; Sorrentino et al., 2013 EMBO Mol Med 5: 1-16), however – mice have very small brains, and so before advancing this treatment into human clinical trials, it is import ant to detennine whether the therapy is effective at treating a much larger brain – that of the Huntaway dog model of this disorder. Dogs will be treated at an age when brain disease has already started, but is not maximal. Treatment involves them getting an injectio n into the bloodstream. Then, how well the treatment is able to get rid of the accumulated heparan sulphate in the brain (and other organs), and how effectively it normalises other aspects of brain disease, will be assessed. Safety aspects of the therapy will also be examined. It is critical that all of this information is gathered before the treatment is given to children with Sanfilippo syndrome type A. A modified form of this treatment approach could also be used for other brain diseases.

– Dr. Kim Hemsley

South Australia Health and Medical Research Institute Adelaide, South Australia