Session Time: 12:00pm-1:30pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: To investigate the potential of nine candidate genes as transcriptional biomarkers of asymptomatic and symptomatic stages of spinocerebellar ataxia type 3 (SCA3).
Background: An abnormally expanded polyglutamine tract in the ataxin-3 protein causes SCA3, the most prevalent spinocerebellar ataxia worldwide. A toxic gain of function, leading to alterations in several cellular mechanisms, namely transcription, was reported for the mutated form of ataxin-3. Disease-modifying compounds have begun being tested in the context of clinical trials; the identification of molecular biomarkers that could be used as outcome measures in such trials is presently a priority.
Methods: Based on a literature search we have listed transcripts/proteins whose expression levels were reported as being altered in SCA3, and selected a subset of genes whose expression was also dysregulated in a previous gene expression study performed by our group. Nine genes (DNAJB1, HSPB1, DNAJB14, DNAJB12, BAX, BCL2, SOD2, IL1β and IL6), which consistently showed the same pattern of dysregulation, were selected to perform quantitative real-time PCR (qPCR). mRNA levels were quantified in blood samples of 36 controls, 16 asymptomatic carriers (AC) and 74 patients. mRNA levels were adjusted for age at blood collection in all statistical procedures. A p-value <0.05 was considered statistically significant.
Results: HSPB1 and BCL2 mRNA adjusted levels were significantly decreased in SCA3 patients compared to controls; BCL2 and IL6 mRNA adjusted levels were significantly decreased in AC compared to controls. DNAJB14 mRNA adjusted levels significantly correlated with disease duration, with patients closer to the age at onset presenting lower expression levels. A tendency for higher BCL2 mRNA adjusted levels was observed in AC closer to predicted age at onset (late AC compared to early AC).
Conclusions: BCL2 seems to be the most promising biomarker of both SCA3 asymptomatic and symptomatic stages; this result should be confirmed in a larger AC cohort, as well as in an independent set of SCA3 subjects.
To cite this abstract in AMA style:M. Raposo, C. Bettencourt, M. Lima. Testing candidate transcriptional biomarkers of asymtpomatic and symptomatic stages in spinocerebellar ataxia type 3 (SCA3) [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/testing-candidate-transcriptional-biomarkers-of-asymtpomatic-and-symptomatic-stages-in-spinocerebellar-ataxia-type-3-sca3/. Accessed September 21, 2023.
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