Mitochondrial DNA depletion in sporadic inclusion body myositis

Charalampos Tzoulis,Novin Balafkan,Hrvoje Miletic,Petter Schandl Sanaker,Gia Tuong Thi Tran,Laurence A Bindoff,Padmanabh S Bhatt

doi:10.1016/j.nmd.2019.02.001

Charalampos Tzoulis, Novin Balafkan + Show 5 more

Open Access

https://doi.org/10.1016/j.nmd.2019.02.001

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Abstract

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.

Highlights

Sporadic inclusion body myositis is a late-onset muscle disease of unknown aetiology [1]
To control for the effects of inflammation and muscle fibre loss, we studied four patients of similar age with late onset necrotising myopathy in which the evolution or pattern of weakness or biopsy were suggestive of Sporadic inclusion body myositis (sIBM)
Four of nine sIBM patients had large numbers of COX-negative fibres, but as can be seen in the table, there is no correlation between the number of COX negative fibres and disease duration

Summary

Introduction

Sporadic inclusion body myositis (sIBM) is a late-onset muscle disease of unknown aetiology [1]. Patients manifest slowly progressive weakness and atrophy that characteristically affects specific muscle groups[1]. The disorder is considered the most common acquired myopathy in the middle-aged and elderly [2] with estimates of prevelance between 3.3 and 5.1 per 100,000 [2,3]. Classified with the inflammatory myopathies, immunomodulatory treatments have been disappointing in controlling disease progression. Patients with co-existent rheumatological diseases such as Sjogrens syndrome or systemic lupus erythematosus, or younger patients with accelerated disease course, may respond to immunomodulatory therapy [2], but evidence suggests the benefit is only short-term [4]. The mainstay of treatment remains non-pharmacological and supportive [5]

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