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Assessment of mitochondrial DNA copy number and common deletion (del4977) as candidate peripheral biomarkers for Spinocerebellar ataxia type 2

LE. Almaguer Mederos, D. Cuello Almarales, R. Aguilera Rodríguez, D. Almaguer Gotay, DO. Palenzuela Gardon, H. Camacho Rodríguez, A. Estupiñán Rodríguez, N. Canales Ochoa, S. Gispert, G. Auburger (Frankfurt am Main, Germany)

Meeting: 2025 International Congress

Keywords: Mitochondrial DNA(mtDNA), Spinocerebellar ataxia

Category: Ataxia

Objective: Assessing the relevance of mtDNA copy number (mtDNAcn) and its common deletion (del4977) as candidate peripheral biomarkers for Spinocerebellar ataxia type 2 (SCA2).

Background: Spinocerebellar ataxia type 2 (SCA2) is a polyglutamine disorder for which there are no disease-modifying treatments. The precise assessment of experimental therapeutic interventions relies upon informative biomarkers of disease severity and progression. It was suggested that mitochondrial function is an important component of pathology for polyglutamine disorders. In particular, mitochondrial DNA copy number and its common deletion (del4977) denotes mitochondrial function and were found altered in several polyglutamine disorders. Nonetheless, the relevance of these two mitochondrial markers for SCA2 is not known.

Method: A study involving 62 SCA2 patients and 63 age and gender-matched control individuals was conducted. Fluorescence-based quantitative PCR was used to determine the relative mtDNAcn and del4977 in leukocytes by relating the expression levels of the mitochondrial ND1 and ND4, and the single-copy nuclear encoded GAPDH genes. The age at disease onset, SARA score, and body mass index were used as clinical outcome variables.

Results: The relative leukocyte mtDNAcn and the amount of del4977 were not significantly associated with age or gender in patients or control individuals. Male patients showed a significant 14.4 percent reduction in the body mass index relative to female patients. The body mass index was correlated with the age at onset and SARA score but showed no significant associations with mtDNAcn or the amount of del4977 in patients or control individuals. Besides, there was no significant correlation between mtDNAcn or the amount of del4977 and markers of disease severity.

Conclusion: The relative leukocyte mtDNAcn and the amount of del4977 are not associated with SCA2 or markers of disease severity, suggesting that these indicators of mitochondrial function might not be relevant as peripheral biomarkers for SCA2. Further studies in additional SCA2 cohorts are needed to account for the potential effects of environmental exposures and population structure.

To cite this abstract in AMA style:

LE. Almaguer Mederos, D. Cuello Almarales, R. Aguilera Rodríguez, D. Almaguer Gotay, DO. Palenzuela Gardon, H. Camacho Rodríguez, A. Estupiñán Rodríguez, N. Canales Ochoa, S. Gispert, G. Auburger. Assessment of mitochondrial DNA copy number and common deletion (del4977) as candidate peripheral biomarkers for Spinocerebellar ataxia type 2 [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/assessment-of-mitochondrial-dna-copy-number-and-common-deletion-del4977-as-candidate-peripheral-biomarkers-for-spinocerebellar-ataxia-type-2/. Accessed October 5, 2025.
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MDS Abstracts - https://www.mdsabstracts.org/abstract/assessment-of-mitochondrial-dna-copy-number-and-common-deletion-del4977-as-candidate-peripheral-biomarkers-for-spinocerebellar-ataxia-type-2/

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