IBM Research

Inclusion body myositis (IBM) is the most common form of myositis in individuals over 50, though it remains a rare condition, with a prevalence of approximately 84 cases per million people over 65. The annual cost of managing IBM is estimated at $35,000. This disease progresses slowly and causes significant muscle disability, primarily affecting the quadriceps and finger flexors. While the underlying mechanisms of IBM are not fully understood, it is characterized by two main histopathological features that indicate both inflammatory (myositis) and degenerative (inclusion body) processes.
Patients with IBM typically show a high presence of differentiated effector CD8+ T cells in their peripheral blood, which invade muscle tissues, alongside a deficiency of systemic CD4+ FoxP3 regulatory T cells. The disease is notably linked to the expression of HLA-DRB1, an autoimmune haplotype, and some patients may also present with anti-cN1A antibodies. However, traditional immunosuppressants have proven ineffective for IBM, and there are currently no established pharmacological treatment guidelines.
The detection of amyloid deposits in muscle fibers suggests that IBM might be primarily a degenerative muscle disorder. Over 80 different proteins, including amyloid β precursor proteins Aβ40 and Aβ42, have been found to aggregate in the muscle fibers of affected patients. Mitochondrial dysfunction and compromised autophagy are also common, leading to the accumulation of p62 and sequestosome 1 aggregates. Thus, IBM can be classified as a proteinopathy, akin to Alzheimer's disease.
Sirolimus, an inhibitor of the mammalian target of rapamycin (mTOR) pathway, plays a crucial role in regulating cell metabolism by integrating nutrient and growth factor signals. By inhibiting mTOR, sirolimus enhances autophagy and mitochondrial function. It is the only drug shown to extend survival in mouse models and has been beneficial for cognitive function in murine models of Alzheimer’s disease. Additionally, sirolimus is used as an immunosuppressant to prevent organ transplant rejection, particularly in kidney transplants, and it encourages the differentiation and expansion of regulatory T cells while suppressing CD8+ and CD4+ effector T-cell populations.
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