Mitochondrial DNA depletion in sporadic inclusion body myositis

• Published in: Neuromuscular disorders : NMD Vol. 29; no. 3; pp. 242 - 246
• Main Authors: Bhatt, Padmanabh S., Tzoulis, Charalampos, Balafkan, Novin, Miletic, Hrvoje, Tran, Gia Tuong Thi, Sanaker, Petter Schandl, Bindoff, Laurence A.
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 01.03.2019
• Subjects: Mitochondrial DNA deletion; Mitochondrial DNA depletion; Necrotising myopathy; Sporadic inclusion body myositis; Mitochondrial DNA depletion; Necrotising myopathy; Mitochondrial DNA deletion; Sporadic inclusion body myositis
• ISSN: 0960-8966; 1873-2364
• DOI: 10.1016/j.nmd.2019.02.001

•Major defect in sIBM is a significant mtDNA depletion.•mtDNA deletions occur in sIBM, but are not universal.•Mitochondrial changes appear to play an important role in sIBM. Sporadic inclusion body myositis (sIBM) is a late onset disorder of unkown aetiology. Mitochondrial changes such as cytochrome oxidase deficient fibres are a well recognised feature and mitochondrial DNA (mtDNA) deletions have also been reported, but not consistently. Since mtDNA deletions are not present in all cases, we investigated whether other types of mtDNA abnormality were responsible for the mitochondrial changes. We studied 9 patients with sIBM. To control for fibre loss or replacement with inflammatory cells, we compared sIBM patients with necrotising myopathy (n = 4) as well as with healthy controls. Qualitative anlysis for mtDNA deletions and quantitative measurement of mtDNA copy number showed that muscle from patients with sIBM contained on average 67% less mtDNA than healthy controls (P = 0.001). The level of mtDNA was also significantly depleted in sIBM when compared to necrotising myopathy. No significant difference in copy number was seen in patients with necrotising myopathy compared to controls. Deletions of mtDNA were present in 4 patients with sIBM, but not all. Our findings suggest that mtDNA depletion is a more consistent finding in sIBM, and one that may be implicated in the pathogenesis of the disease.