The inherited Spinocerebellar ataxias (SCAs) are a broad group of inherited neurodegenerative diseases characterized by selective cerebellar degeneration and other neurological symptoms. In South Africa, the main research focus has been on SCA type 7. This disorder is dominantly inherited and caused by the expansion of a CAG repeat in the ataxin-7 gene. The translation of this repeat leads to an extended polyglutamine tract within the downstream protein, resulting in SCA7 being classified as a polyglutamine repeat disorder. The SCA7 project aims to investigate the molecular pathogenesis of SCA7 through the generation of patient-derived disease-relevant cell types (neuronal cells, RPE and photoreceptors differentiated from iPSCs), with a view to developing and refining gene-silencing therapies for the disease. The iPSC-derived models generated will thus also be used as pre-clinical cellular models, to determine therapeutic efficacy and safety, in preparation for future clinical trials.
The inherited ataxia group is led by Professor Jacquie Greenberg. Drs Lauren Watson and Danielle Smith completed their PhDs in the ataxia group, focussing on the development of iPSC-derived neuronal and photoreceptor models of SCA7. In 2014 Dr Robea Ballo and Sylvia Kamanzi-Wa joined the project. Sylvia is completing a PhD project to investigate the involvement of RPE in SCA7 pathogenesis.
Visit the Human Genetics website for more information.
References:
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Greenberg LJ, Smith DC, Burman RJ, Ballo R, Kidson SH (2015). Towards guidelines for informed consent for prospective stem cell research. South African Journal of Bioethics and Law (8, Suppl 1) 46-48.
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Scholefield J, Watson L, Smith D, Greenberg LJ, Wood MJA (2014). Allele-specific silencing of mutant Ataxin-7 in SCA7 patient-derived fibroblasts. European Journal of Human Genetics (22) 1369-1375.
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Greenberg LJ, Smith DC, Pope A (2013). Stem cells on South African shores: proposed guidelines for comprehensive informed consent. S Afr Med J (103)1:6.
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Ballo R, Greenberg LJ, Kidson S (2013). A New Class of Stem Cells in South Africa: Introducing Induced Pluripotent Stem cells (iPS cells). S Afr Med J (103)1:16-17.
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Watson L, Scholefield J, Greenberg J, Wood M (2012). Polyglutamine disease: from pathogenesis to therapy. S Afr Med J Centenary Edition. S Afr Med J (102) 6: 481-484.
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Watson LM, Wood MJ (2012). RNA therapy for polyglutamine neurodegenerative diseases. Expert Rev Mol Med. Jan 31;14:e3.
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Smith DC, Bryer A, Watson LM, Greenberg LJ (2012). The inherited polyglutamine Spinocerebellar ataxias in South Africa. S Afr Med J. . (102) 8: 683-686.
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Scholefield J, Wood MJ (2010). Therapeutic gene silencing strategies for polyglutamine disorders. Trends Genet. 26(1):29-38.
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Scholefield J, Greenberg LJ, Weinberg MS, Arbuthnot PB, Abdelgany A, Wood MJA (2009). Design of RNAi Hairpins for Mutation-Specific Silencing of Ataxin-7 and Correction of a SCA7 Phenotype. PLoS ONE. 4(9): e7232.
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Greenberg J, Solomon G, Vorster A, Heckmann J, Bryer A (2006). Origin of the SCA7 gene mutation in South Africa: implications for molecular diagnostics. Clin Genet 70(5):415-417.
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Bryer A, Krause A, Bill P, Davids V, Bryant D, Butler J, Heckmann J, Ramesar R, Greenberg J (2003). The hereditary adult-onset ataxias in South Africa. J Neurol Sci 216(1):47-54.
