Abstracts
A simple approach to gene therapy for Sanfilippo Syndrome
Chantelle McIntyre
PhD student, University of Adelaide, Discipline of Paediatrics
Supervised through Genetic Medicine, CYWHS
Genes are composed of a molecule called DNA. They are inherited from our parents, and act as instruction manuals for our bodies to make other molecules called proteins. Proteins enable the cell to perform essential functions; for example, a protein called sulphamidase is required by the cell to break down complex carbohydrates called mucopolysaccharides.
Mucopolysaccharidosis type IIIA (MPS IIIA) develops when the instructions in the sulphamidase gene are changed, or "mutated". The mutated sulphamidase protein cannot perform its task normally, and consequently, mucopolysaccharides accumulate excessively. Progressive swelling of the cells with stored material disrupts their delicate architecture and they no longer function normally. Children who inherit MPS IIIA usually die within their teenage years because the central nervous system (CNS) progressively deteriorates. Milder symptoms of the disease present in other tissues, primarily the liver and spleen.
Currently there is no clinical treatment available for MPS IIIA. To treat MPS IIIA we have isolated normal sulphamidase DNA and packaged it into a delivery vehicle made from a disabled virus. Using an animal (mouse) model of the disease, we have demonstrated that delivery of the sulphamidase gene into young affected mice using a very simple method (intravenous injection) stops the disease from manifesting in the liver, spleen, kidney, heart, and most interestingly, has a beneficial effect on the CNS. This technology is known as gene therapy. We are confident that a more complete correction of MPS IIIA disease can be achieved by increasing the amount of sulphamidase protein produced by the functional sulphamidase DNA.
