Sunday 11th September

Keynote lecture

S001 GENETICS, HISTORY, AND HUNTINGTON’S DISEASE

P. S. Harper.University Department of Genetics, Cardiff University, UK

An historical perspective can throw valuable light on how our understanding has progressed over the years, not just for Huntington’s disease (HD) itself, but for a range of other genetic and neurological disorders. The history of the condition is of interest in its own right, but less explored historically have been the genetics of HD as a pioneer in gene mapping and gene isolation, the experience of predictive testing as a worldwide endeavour, and HD as a model for social issues, such as insurance.

In each of these aspects, HD has led the way and our experience from it has been widely generalisable. Now we are starting to see the same process in relation to therapeutic initiatives and worldwide collaborative trials. The history of all these successive developments may well confirm the key role that HD, through the patients, families, and professionals involved, has had in the wider development of our understanding of the basis and consequences of inherited disease.

Keywords: history; genetics; therapeutic trials

Plenary session I: pathogenic mechanisms 1

S002 PATHOGENIC MECHANISMS IN HUNTINGTON’S DISEASE: CLUES TO POSSIBLE THERAPEUTIC STRATEGIES

D. C. Rubinsztein¹, B. Ravikumar¹, C. Vacher¹, S. Luo¹, J. Davies¹, Z. Berger¹, C. O’Kane², S. Imarisio², A. Acevedo-Arozena³, S. D. M. Brown³.¹Department of Medical Genetics, Cambridge Institute for Medical Research, Addenbrooke’s Hospital, Cambridge, UK; ²Department of Genetics, University of Cambridge, UK; ³Medical Research Council Mammalian Genetics Unit, Harwell, UK

The Huntington’s disease mutation is likely to cause disease predominantly by gain-of-function mechanisms. A number of processes may contribute to the toxicity of the mutation, including aggregation, raised levels of reactive oxygen species, abnormal calcium signalling, and perturbed axonal transport. Thus, it may be difficult to effectively treat the disease by …