[Inclusion body myositis--a rarely recognized disorder]

Area of Science:

• Neurology
• Immunology
• Pathology

Context:

• Inclusion body myositis (IBM) is the most prevalent disabling inflammatory myopathy affecting individuals over 50, particularly men.
• IBM presents with both inflammatory and degenerative muscle pathology, characterized by T-cell mediated autoimmunity and protein aggregate deposition.
• The disease progresses slowly, often diagnosed years after symptom onset, with characteristic asymmetric muscle weakness.

Purpose:

• To review the current understanding of inclusion body myositis (IBM) pathophysiology.
• To evaluate the efficacy of existing and experimental treatments for IBM.
• To identify therapeutic strategies that address both inflammatory and degenerative aspects of IBM.

Summary:

• IBM involves cytotoxic CD8-positive T-cells invading muscle fibers, alongside protein aggregate formation and vesicular changes.
• Diagnosis relies on muscle biopsy, as clinical presentation can be variable.
• Existing treatments like prednisone, azathioprine, methotrexate, and IVIG have shown limited or no efficacy, while oxandrolone failed to improve symptoms.

Impact:

• A small study using alemtuzumab, a T-cell depleting antibody, demonstrated a six-month slowdown in disease progression.
• Muscle biopsies post-alemtuzumab treatment showed reduced T-cells and suppressed degeneration markers.
• Future effective therapies must target both the inflammatory T-cell response and the degenerative proteinopathy in IBM.