1st Year Research Reviews—2016

ML II

Dr. Kim Hemsley, Dr. Alessandro Fraldi, and Professor Robert D. Jolly
Lysosomal Diseases Research Unit
Adelaide, SA, Australia

“AAV2/8 medicated expression of modified sulphamidase: Liver targeting for improved secretion and brain deliver. Pre-clinical study in the Huntaway dog”

Summary

We are carrying out a pre-clinical trial of a new gene therapy approach for Sanfilippo syndrome (MPS IIIA). The treatment has previously been tested in mice with this disorder (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 important to determine whether the therapy is effective at treating a much larger brain. We have chosen to use the MPS IIIA Huntaway dog model. To date, a total of six dogs have been given an intravenous (blood) injection of the treatment at an age at which brain disease has already started (< 6 months of age), but is not maximal. A further six dogs (three unaffected, three affected) will serve as controls. The next phase of the study will determine whether the gene therapy approach has been able to get rid of the accumulated heparan sulphate in the brain (and other organs), and whether it normalises other aspects of brain disease. 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.