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H D I N S I G H T S HD Research Around the World: Australia HD Down Under By: Izelle Labuschagne, PhD Approximately 1,200 Australians have HD and 6,000 people are at risk1. HD got its start in our island state of Tasmania, where it was first introduced in 1842 by a woman from Somerset, England, who had 13 children, 11 of whom carried the HD gene. The 1970s in Australia saw significant early developments for HD, thanks to psychiatrist and educator Professor Edmond Yu-Kuen Chiu. In 1972, Professor Chiu envisioned a plan that would eventually result in the opening of the first HD clinic in Australia at the Royal Melbourne Hospital, followed by his establishment in 1973 of the Australian HD Association. Since then, many more clinical services for HD have been established in other Australian states. Our largest HD research efforts come from Melbourne-based researchers. Biochemist Dr. Danny Hatters from the University of Melbourne's Bio21 Institute leads a team studying how clumps of huntingtin (Htt) form, and their role in disease pathogenesis. Dr Hatters' group has developed tools for dissecting how Htt clumps accumulate at the molecular level. For example, sedimentation velocity analysis can measure the size and heterogeneity of all Htt molecules in a cell extract2,3. Another more recently developed method can, for the first time, separate and recover cells enriched with mutant Htt in dispersed patterns relative to Htt in inclusions4, which allows detailed study of the aggregation and clumping process and how it relates to biological functioning of the cells that contain mutant Htt (Figure 1). Professor Anthony Hannan and his team at the Florey Institute of Neuroscience and Mental Health in Melbourne have made exciting discoveries using the R6/1 transgenic mouse model of HD. A key discovery from their work was the finding that environmental enrichment has beneficial effects on the development of HD in the transgenic mice. Environmental enrichment resulted in a delay in onset and a slowing of disease progression in the mice5, and it also resulted in the rescue of abnormal stress response in the adrenal cells6 (Figure 2). Furthermore, increased physical activity delayed motor onset and slowed cognitive decline7. Hannan's team was the first to demonstrate the beneficial effects of environmental stimulation in a genetic model of a brain disorder. These, and other findings from Hannan's lab, provide a biological foundation for the potential of environmental enrichment as a treatment option for HD. Our focus at Monash University in Melbourne is on clinical studies assessing cognition and structural brain changes in HD. Our work is well-integrated with the largest HD clinic in the state, run by Dr. Andrew Churchyard at the Calvary-Bethlehem Hospital. (continued on Page 10...) Figure 1. A new approach developed by Dr Hatters' research team that enables cells with inclusions to be separated from those without4. a) The technique uses pulse shape information from a flow cytometer to separate diffuse patterns of Htt from inclusions. b) Analysis of a normal polyglutamine length (25Q) versus a HD length (46Q) shows a new population of cells (i), that have inclusions, as distinct from cells that have diffuse Htt (ni). c) The enrichment of these cells was verified by microscopy. If you are interested in contributing a piece that highlights research in your part of the world, please contact us at editor@hdinsights.org. HD Insights, Vol. 5 Copyright © Huntington Study Group 2013. All rights reserved. 9

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