World Customs Organization (WCO)

Vollständiger Abstract

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PURPOSE OF REVIEW: Inclusion body myositis (IBM) is the most prevalent acquired myopathy in adults over 50 years of age, yet effective disease-modifying therapy has remained elusive. The longstanding debate over whether degeneration or inflammation is the primary driver has now given way to a model of bidirectional interplay. This review critically appraises advances published between January 2025 and June 2026, encompassing molecular pathomechanisms, early diagnostic strategies, disease-modifying therapies, and rehabilitation. RECENT FINDINGS: A pivotal mechanistic advance is the demonstration that TDP-43 nuclear depletion in IBM myonuclei generates cryptic exon-derived neoantigens that directly activate CD8+ T cells, molecularly unifying cell-autonomous degeneration and adaptive immune activation. In parallel, mitochondrial DNA leakage activates the cGAS-STING innate immune pathway prior to T cell infiltration. An endogenous compensatory mechanism involving the NORAD-Pumilio regulatory axis has also been identified. Clinically, preliminary data from the Phase 2/3 MUSCLE trial suggest a potential 50% slowing of progression in mild-to-moderate IBM with the anti-KLRG1 antibody ulviprubart, pending full peer-reviewed publication, while novel diagnostic and rehabilitation strategies further advance personalized care. SUMMARY: A molecular cascade from cell-autonomous TDP-43 dysfunction to cryptic epitope-driven immune activation could underlie the pathogenesis of IBM. Personalized multidisciplinary care integrating early diagnosis, targeted disease-modifying therapy, and advanced rehabilitation represents the emerging treatment paradigm.

Abstract: PubMed · Datensatz