Keetch Mecham

Background: Inclusion Body Myositis (IBM) is a rare, slow progressing, inflammatory myopathy characterized by weakness and atrophy of distal and proximal muscles, with muscles of the long finger flexors and quadriceps muscles being first affected, and often accompanied by difficulty swallowing ^{[4] [13]}. It is the most common acquired myopathy in patients older than 50 years of age ^[4]. IBM is defined by inflammatory infiltrates, rimmed vacuoles, and protein aggregates on histopathology ^[13]. No effective treatment of IBM has been identified so far, however different regimens including steroids, monoclonal antibodies, methotrexate, and many other treatments have been studied ^[5]. Though previously clinicians have believed that exercise would increase inflammation and accelerate disease progression, data shows that exercise actually promotes a general anti-inflammatory response and is both safe and effective in slowing the progression of IBM ^{[1][3][6][9][10][11][17]}.

Methods: A PubMed search was performed using key terms such as “Pathology of Inclusion Body Myositis”,  “Exercise in Inclusion Body Myositis”, and “Anti-inflammatory effects of exercise”, and was filtered to emphasize studies published within 5 years from the time of this review.

Results: Exercise has been consistently demonstrated to systemically reduce inflammation in the body over time. Recent studies are helping us understand the implications that exercise has in management of inclusion body myositis. Studies at the basic science level are helping us to understand the mechanisms by which exercise exerts an anti-inflammatory and immunomodulatory response on a systemic level, and at the muscle fiber level ^[6][11] . Meanwhile, clinical trials are making clearer the role that exercise should play at a clinical level in management of IBM, with new studies revealing that exercise can delay muscle degeneration ^{[1] [3] [9] [10] [17]}.

Conclusions: Inclusion Body Myositis remains a rare myopathy with no effective treatment. While many different avenues for treatment have been explored, few have shown promise in practical treatment of the disease. While it is important to continue to study the pathogenesis and explore various therapies targeted at interrupting the pathophysiology of the disease, there is a growing body of data that suggests that exercise can provide protective benefits for patients with IBM, ultimately slowing the disease progression and providing the patients with an important method for management of this lifelong, debilitating disease ^{[1][3][5][9][10][17]}. Future research should be targeted to cement the use of exercise in management of IBM, understand how exercise affects pathophysiology of IBM, identify protocols that can be implemented by patients with IBM, and educate providers to dispel old assumptions surrounding exercise and IBM.

Works Cited:

1. Alexanderson, H. (2012). Exercise in inflammatory myopathies, including inclusion body myositis. Current rheumatology reports, 14, 244-251.
2. Cantó-Santos, J., Valls-Roca, L., Tobías, E., García-García, F. J., Guitart-Mampel, M., Andújar-Sánchez, F., … & Garrabou, G. (2025). Human induced pluripotent stem cell-derived myotubes to model inclusion body myositis. Acta Neuropathologica Communications, 13(1), 38.
3. D’Alton, C., Johnstone, R., du Plessis, C., Pursad, A., & Kohn, T. A. (2022). The effect of systematic exercise training on skeletal muscle strength in a patient with advanced inclusion body myositis: A case study. South African Journal of Sports Medicine, 34(1), 1-3.
4. Dalakas, M. C. (2006). Sporadic inclusion body myositis—diagnosis, pathogenesis and therapeutic strategies. Nature clinical practice Neurology, 2(8), 437-447.
5. Glaubitz, S., Zeng, R., & Schmidt, J. (2020). New insights into the treatment of myositis. Therapeutic Advances in Musculoskeletal Disease, 12, 1759720X19886494.
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7. Greenberg, S. A. (2019). Inclusion body myositis: clinical features and pathogenesis. Nature Reviews Rheumatology, 15(5), 257-272.
8. Greenberg, S. A., Pinkus, J. L., Kong, S. W., Baecher-Allan, C., Amato, A. A., & Dorfman, D. M. (2019). Highly differentiated cytotoxic T cells in inclusion body myositis. Brain, 142(9), 2590-2604.
9. Jørgensen, A. N., Aagaard, P., Frandsen, U., Boyle, E., & Diederichsen, L. P. (2018). Blood-flow restricted resistance training in patients with sporadic inclusion body myositis: a randomized controlled trial. Scandinavian Journal of Rheumatology, 47(5), 400-409.
10. Jørgensen, A. N., Jensen, K. Y., Nielsen, J. L., Frandsen, U., Hvid, L. G., Bjørnshauge, M., … & Aagaard, P. (2022). Effects of blood‐flow restricted resistance training on mechanical muscle function and thigh lean mass in sIBM patients. Scandinavian journal of medicine & science in sports, 32(2), 359-371.
11. Langston, P. K., Sun, Y., Ryback, B. A., Mueller, A. L., Spiegelman, B. M., Benoist, C., & Mathis, D. (2023). Regulatory T cells shield muscle mitochondria from interferon-γ–mediated damage to promote the beneficial effects of exercise. Science immunology, 8(89), eadi5377.
12. Li, Y., Chen, W., Ogawa, K., Koide, M., Takahashi, T., Hagiwara, Y., … & Kanzaki, M. (2022). Feeder-supported in vitro exercise model using human satellite cells from patients with sporadic inclusion body myositis. Scientific Reports, 12(1), 1082.
13. Lindgren, U., Pullerits, R., Lindberg, C., & Oldfors, A. (2022). Epidemiology, survival, and clinical characteristics of inclusion body myositis. Annals of Neurology, 92(2), 201-212.
14. Naddaf, E. (2022). Inclusion body myositis: update on the diagnostic and therapeutic landscape. Frontiers in Neurology, 13, 1020113.
15. Naddaf, E., Barohn, R. J., & Dimachkie, M. M. (2018). Inclusion body myositis: update on pathogenesis and treatment. Neurotherapeutics, 15(4), 995-1005.
16. Pinto, M. V., Laughlin, R. S., Klein, C. J., Mandrekar, J., & Naddaf, E. (2022). Inclusion body myositis: correlation of clinical outcomes with histopathology, electromyography and laboratory findings. Rheumatology, 61(6), 2504-2511.
17. Spector, S. A., Lemmer, J. T., Koffman, B. M., Fleisher, T. A., Feuerstein, I. M., Hurley, B. F., & Dalakas, M. C. (1997). Safety and efficacy of strength training in patients with sporadic inclusion body myositis. Muscle & Nerve: Official Journal of the American Association of Electrodiagnostic Medicine, 20(10), 1242-1248.