Clinical efficacy of haematopoietic stem cell transplantation in mucopolysaccharidosis IIIA [ 2007 - 2009 ]

Research Grant

Researchers: Prof John Hopwood (Principal investigator) ,  Dr Kim Hemsley ,  Gouri Yogalingam

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', 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. Mucopolysaccharidosis (or MPS) type IIIA is a LSD that affects the brain. Bone marrow transplantation (BMT) is an accepted treatment for many diseases, including cancer. However, unlike cancer and some LSD, BMT does not work in MPS IIIA children. The reasons for this are unknown. This project is important in understanding the basic mechanisms that prevent this form of therapy from working in these children. If we can understand what prevents its effectiveness, we can devise methods to overcome it and potentially offer MPS IIIA (and other LSD that do not respond to BMT) a viable treatment option. We have a colony of mice affected by MPS IIIA; their symptoms are similar to that seen in humans, making them ideal for this study.

Funding Amount $AUD 508,051.76

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant