Exploring challenges in the management and treatment of inclusion body myositis

Skolka, Michael P.; Naddaf, Elie

doi:10.1097/bor.0000000000000958

Cited by 9 publications

(15 citation statements)

References 123 publications

(132 reference statements)

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“…Disease progression is usually slow. Variability in the clinical presentation and a lack of specific features/muscle involvement in some patients represent challenges for a prompt and correct diagnosis, making laboratory tests and histological analysis of muscle biopsy fundamental tools in the diagnostic workup [ 7 ].…”

Section: Diagnosis Of Sibmmentioning

confidence: 99%

“…The disease presents with muscle weakness mainly affecting the quadriceps and finger flexors [ 6 ]. At present, there are no disease-modifying therapies for this progressive disease that eventually leads to severe disability [ 7 ]. Despite common clinical characteristics, the phenotype can be variable, and the diagnosis relies on the combination of clinical evaluation, laboratory tests, and pathologic changes in muscle biopsy [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

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Sporadic Inclusion Body Myositis at the Crossroads between Muscle Degeneration, Inflammation, and Aging

Guglielmi,

Cheli,

Tonin

et al. 2024

IJMS

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Sporadic inclusion body myositis (sIBM) is the most common muscle disease of older people and is clinically characterized by slowly progressive asymmetrical muscle weakness, predominantly affecting the quadriceps, deep finger flexors, and foot extensors. At present, there are no enduring treatments for this relentless disease that eventually leads to severe disability and wheelchair dependency. Although sIBM is considered a rare muscle disorder, its prevalence is certainly higher as the disease is often undiagnosed or misdiagnosed. The histopathological phenotype of sIBM muscle biopsy includes muscle fiber degeneration and endomysial lymphocytic infiltrates that mainly consist of cytotoxic CD8+ T cells surrounding nonnecrotic muscle fibers expressing MHCI. Muscle fiber degeneration is characterized by vacuolization and the accumulation of congophilic misfolded multi-protein aggregates, mainly in their non-vacuolated cytoplasm. Many players have been identified in sIBM pathogenesis, including environmental factors, autoimmunity, abnormalities of protein transcription and processing, the accumulation of several toxic proteins, the impairment of autophagy and the ubiquitin–proteasome system, oxidative and nitrative stress, endoplasmic reticulum stress, myonuclear degeneration, and mitochondrial dysfunction. Aging has also been proposed as a contributor to the disease. However, the interplay between these processes and the primary event that leads to the coexistence of autoimmune and degenerative changes is still under debate. Here, we outline our current understanding of disease pathogenesis, focusing on degenerative mechanisms, and discuss the possible involvement of aging.

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Section: Diagnosis Of Sibmmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sporadic Inclusion Body Myositis at the Crossroads between Muscle Degeneration, Inflammation, and Aging

Guglielmi,

Cheli,

Tonin

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…Typically occurring after the age of 50 ( Snedden et al, 2022 ), sIBM is characterized by progressive and asymmetric weakness in the quadriceps and long finger flexors rather than an acute or subacute symmetrical proximal muscle weakness seen in other subtypes of IIM ( Zubair et al, 2023 ). Individuals with sIBM experience a loss of muscle strength at a rate of 3.5%–28% per year ( Zubair et al, 2023 ) and can become wheelchair-bound at a median time of 10.5 years after the disease onset ( Skolka and Naddaf, 2023 ). Respiratory compromise and dysphagia are common risk factors for premature death in sIBM patients, which may account for their slight but significantly shortened lifespan when compared to healthy subjects ( Shelly et al, 2021 ).…”

Section: Symptoms Diagnosis and Current Treatment Of Sibmmentioning

confidence: 99%

“…They are often administrated with other immunosuppressants like azathioprine and methotrexate to reduce steroid-related side effects like osteoporosis and cardiovascular diseases ( Oddis, 2016 ). Second-line treatments such as cyclosporine, tacrolimus, and intravenous immunoglobin are used to alleviate the disease symptoms in refractory or severe PM and DM cases ( Zeng et al, 2022 ; Skolka and Naddaf, 2023 ). Nonetheless, these immunosuppressive agents are not enduringly effective in treating some IIM patients, particularly those with sIBM ( Skolka and Naddaf, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

“…Second-line treatments such as cyclosporine, tacrolimus, and intravenous immunoglobin are used to alleviate the disease symptoms in refractory or severe PM and DM cases ( Zeng et al, 2022 ; Skolka and Naddaf, 2023 ). Nonetheless, these immunosuppressive agents are not enduringly effective in treating some IIM patients, particularly those with sIBM ( Skolka and Naddaf, 2023 ). A recent study using human sIBM xenografts demonstrated that T cell depletion does not alleviate the muscle degenerative features ( Britson et al, 2022 ), further challenging the pathogenic role of inflammation in the disease.…”

Section: Introductionmentioning

confidence: 99%

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Mitochondrial defects in sporadic inclusion body myositis—causes and consequences

Iu,

So,

Chan

2024

Front. Cell Dev. Biol.

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Sporadic inclusion body myositis (sIBM) is a distinct subcategory of Idiopathic Inflammatory Myopathies (IIM), characterized by unique pathological features such as muscle inflammation, rimmed vacuoles, and protein aggregation within the myofibers. Although hyperactivation of the immune system is widely believed as the primary cause of IIM, it is debated whether non-immune tissue dysfunction might contribute to the disease’s onset as patients with sIBM are refractory to conventional immunosuppressant treatment. Moreover, the findings that mitochondrial dysfunction can elicit non-apoptotic programmed cell death and the subsequent immune response further support this hypothesis. Notably, abnormal mitochondrial structure and activities are more prominent in the muscle of sIBM than in other types of IIM, suggesting the presence of defective mitochondria might represent an overlooked contributor to the disease onset. The large-scale mitochondrial DNA deletion, aberrant protein aggregation, and slowed organelle turnover have provided mechanistic insights into the genesis of impaired mitochondria in sIBM. This article reviews the disease hallmarks of sIBM, the plausible contributors of mitochondrial damage in the sIBM muscle, and the immunological responses associated with mitochondrial perturbations. Additionally, the potential application of mitochondrial-targeted chemicals as a new treatment strategy to sIBM is explored and discussed.

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Inclusion body myositis: Correcting impaired mitochondrial and lysosomal autophagy as a potential therapeutic strategy

Brady,

Poulton,

Muller

2024

Autoimmunity Reviews

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Exploring challenges in the management and treatment of inclusion body myositis

Cited by 9 publications

References 123 publications

Sporadic Inclusion Body Myositis at the Crossroads between Muscle Degeneration, Inflammation, and Aging

Sporadic Inclusion Body Myositis at the Crossroads between Muscle Degeneration, Inflammation, and Aging

Mitochondrial defects in sporadic inclusion body myositis—causes and consequences

Inclusion body myositis: Correcting impaired mitochondrial and lysosomal autophagy as a potential therapeutic strategy

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