Canine adenovirus-mediated gene therapy for CNS pathology in LSD [ 2006 - 2008 ]

Research Grant

Researchers: Prof John Hopwood (Principal investigator) ,  Dr Eric Kremer ,  Dr Kim Hemsley

Brief description Lysosomal storage disorders (LSD) are inherited diseases that affect about 1 in 7700 Australian children; all share common physical symptoms include heart and breathing difficulties, stiff joints, skeletal deformities, enlarged head, and a characteristic facial appearance. Two-thirds of patients will also develop brain disease. The lysosome is a component of each cell in the human body; its role it is to break down and remove waste from the cell. This involves a series of proteins (enzymes) that act in sequence. A LSD arises when the lysosome lacks the activity of one protein in this chain. This loss of protein activity means that the waste removal process is impaired. Waste begins to 'store' in the lysosome, clogging the cell and interfering with its usual functions. This gives rise to devastating symptoms that worsen over time as storage increases. Brain disease in LSD has profound effects on the child: mental capacity declines, they become hyperactive and aggressive and progressively lose learned skills (e.g. walking, talking) and control of bodily functions. Artifically made protein is being successfully used to treat some LSD via intravenous injection. However, it cannot access the brain because of a protective barrier that surrounds it. Gene therapy is a method by which we are attempting to overcome this problem. By using a virus called canine adenovirus (or CAV), we plan to produce and insert the missing protein into mice who are deficient in it. CAV will be the protein carrier. CAV is safe in humans and does not have many of the problems associated with some other viruses being tested in gene therapy. We have diagnosed mice who are naturally affected by a LSD with brain disease called MPS IIIA. Their symptoms are similar to that seen in humans, making them ideal for study. CAV vectors are being considered as a long-term treatment for patients who suffer from MPS IIIA and other degenerative brain diseases.

Funding Amount $AUD 490,029.35

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant