The new millennium.

Inherited neurodegenerative diseases, characterised by progressive symptoms and a lengthy disease course, present a significant economic and psychological burden to affected families. The Department (now Division) of Human Genetics at the University of Cape Town (UCT) has a long history of research into these conditions, beginning under the leadership of Prof. Peter Beighton in 1972. This research has focused primarily on the polyglutamine (polyQ) diseases, a subset of monogenic neurodegenerative diseases with a well-defined genetic aetiology, which includes Huntington’s disease (HD) and six of the spinocerebellar ataxias (SCA1, 2, 3, 6, 7 and 17).[1] Complementing the work done in the research laboratories, an internationally accepted counselling and testing protocol for these conditions has been offered by the Division’s clinical service, and latterly, in conjunction with the National Health Laboratory Service (NHLS), since 1995.[2] Seminal work by Michael Hayden, under Beighton’s mentorship, provided the first comprehensive survey of HD in South Africa (SA) in 1979.[3] This laid the foundation for a number of MSc and PhD projects exploring the molecular basis of HD, including that of Jacquie Greenberg, herself now Professor of Human Genetics at UCT. In 2013, UCT researchers, in collaboration with Hayden (now University Killam Professor at the Department of Medical Genetics, University of British Columbia) and others, identified novel, ethnically distinct haplotypes among SA HD patients, providing the first evidence for multiple origins of the disease-causing mutation within the black SA population.[4] These findings are likely to have significant implications for future therapies.[5] (The history of HD research in Africa is reviewed elsewhere in this issue by Baine et al.) Research into the polyQ SCAs at UCT was initiated by Alan Bryer, who completed his PhD on ‘The Inherited Ataxias in SA’ in 1994. Subsequent work, by Bryer and others, traced the origin and epidemiology of the polyQ SCA mutations in SA, identifying founder effects in two of the SCAs (SCA1 and 7), which may extend to neighbouring countries.[6-9] SCA7, in particular, has been the focus of concerted local research efforts over the past 10 years. The unusually high frequency of this condition in the SA population, coupled with unique phenotypic characteristics, make it an attractive prospect for therapeutic development. Research into the disease has since progressed from early molecular geneticsbased investigations to the development of cutting-edge stem cell models and gene-silencing therapies, in an effort to better understand and treat the disease.