Towards a Clinical Trial of Gene Therapy for Mucopolysaccharidosis VI

Mucopolysaccharidosis VI (MPS VI) is caused by deficient arylsulfatase B (ARSB) activity, resulting in lysosomal storage of glycosaminoglycans (GAGs). MPS VI is characterized by dysostosis multiplex, organomegaly, corneal clouding, and heart valve thickening without central nervous system involvement. Enzyme replacement therapy for MPS VI has limited efficacy and requires multiple administrations of costly enzymes. Gene transfer to a factory organ like liver may provide a life-time source of secreted ARSB. We have shown that single intravascular administration of adeno-associated viral vectors (AAV) 2/8-TBG-ARSB in MPS VI cats results in long-term ARSB expression, the clearance of GAG storage, the improvement of long bone length, the reduction of heart valve thickness, and the improvement of spontaneous mobility. These promising results prompted us to plan a clinical trial to investigate this strategy in MPS VI patients. The clinical trial is ongoing at the Federico II University of Naples. The first three subjects have been enrolled and treated with the starting dose; based on safety data, two more subjects were enrolled and treated with the high dose of vector. To date, the infusion of the gene therapy vector was well-tolerated in all subjects without changes in the vital signs during the infusion. Laboratory parameters and clinical conditions remained stable in the weeks after gene therapy. So, the data collected so far support the safety of the therapy. The "Total Award" amount indicated for this project represents the share of the funding of the Telethon Foundation for research by the Tigem institute from July 2016 until last budget year, calculated based on the size of the research group.