Molecular Dx Landmark-class

Systemic Amyloidosis: Advances in Mass Spectrometry Typing and Diagnostic Imaging

This Lancet seminar reviews the evolving diagnostic landscape for systemic amyloidoses, highlighting laser capture and mass spectrometry from fixed tissue as the gold standard for amyloid fibril typing. The increasing recognition of wild-type transthyretin cardiac amyloidosis is driven by cardiac MRI and repurposed bone scintigraphy tracers. Early diagnosis remains the critical unmet need, while emerging therapies including RNA inhibitors, stabilizers, and immunotherapies hold promise for improved outcomes.

The original study

Systemic amyloidosis.

Authors
Wechalekar AD, Gillmore JD, Hawkins PN
Journal
Lancet (London, England)
Type
Journal Article, Review
PMID
26719234
Read the original study →

Original abstract

Tissue deposition of protein fibrils causes a group of rare diseases called systemic amyloidoses. This Seminar focuses on changes in their epidemiology, the current approach to diagnosis, and advances in treatment. Systemic light chain (AL) amyloidosis is the most common of these conditions, but wild-type transthyretin cardiac amyloidosis (ATTRwt) is increasingly being diagnosed. Typing of amyloid fibrils, a critical determinant of therapy, has improved with the wide availability of laser capture and mass spectrometry from fixed histological tissue sections. Specific and accurate evaluation of cardiac amyloidosis is now possible using cardiac magnetic resonance imaging and cardiac repurposing of bone scintigraphy tracers. Survival in AL amyloidosis has improved markedly as novel chemotherapy agents have become available, but challenges remain in advanced disease. Early diagnosis, a key to better outcomes, still remains elusive. Broadening the amyloid-specific therapeutic landscape to include RNA inhibitors, fibril formation stabilisers and inhibitors, and immunotherapeutic targeting of amyloid deposits holds promise to transform outcomes in systemic amyloidoses.