TTR Antibody
Description
Definition and Biological Rationale
TTR antibodies are immunoglobulins designed to bind conformational epitopes exposed in misfolded or aggregated TTR. Unlike normal tetrameric TTR, pathogenic forms (monomers, oligomers, or fibrils) expose cryptic regions such as residues 39–44, 89–97, or 115–124, which serve as antibody targets . Their primary functions include:
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Fibrillization inhibition: Blocking TTR self-assembly into amyloid structures
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Immune clearance: Promoting macrophage phagocytosis of TTR aggregates
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Diagnostic utility: Detecting circulating misfolded TTR for disease monitoring
Key Antibody Types and Epitope Specificity
Preclinical Studies
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RT24: Reduced TTR deposits by 60–75% in FAP model rats after 6-month administration, with no adverse effects on liver or renal function . Demonstrated fibril inhibition at 1:100 antibody:TTR molar ratio .
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NI006: Showed nanomolar affinity for TTR fibrils (>100x selectivity over tetramers) in competitive ELISA . Enhanced macrophage uptake by 3.8-fold compared to controls .
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PRX004: Inhibited fibril formation at substoichiometric concentrations (10 nM antibody vs. 1 μM TTR) .
Clinical Observations
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Diagnostic potential: Anti-TTR (39–44) antibodies detected amyloidogenic TTR in 92% of ATTRv patients vs. 0% in controls .
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Cardiac amyloidosis: A monoclonal antibody reduced cardiac pyrophosphate signals by 40% in wild-type ATTR models, improving ejection fraction by 12% .
Emerging Diagnostic Applications
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ELISA-based detection:
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Plasma biomarker quantification: Aggregated TTR levels correlate with disease progression (r=0.78, p<0.01)
Challenges and Future Directions
Current limitations include epitope heterogeneity across TTR variants and blood-brain barrier penetration for CNS targets. Next-generation antibodies are exploring:
Product Specs
Product Science Overview
Transthyretin (TTR), also known as prealbumin, is a protein primarily synthesized in the liver and choroid plexus of the brain. It functions as a transport protein for thyroxine (T4) and retinol (vitamin A) by forming a complex with retinol-binding protein . TTR is a homo-tetrameric protein, meaning it consists of four identical subunits .
TTR plays a crucial role in the transport of thyroid hormones and vitamin A, which are essential for various physiological processes, including metabolism, growth, and development . Additionally, TTR is involved in other intracellular processes such as proteolysis, nerve regeneration, autophagy, and glucose homeostasis .
Mouse anti-human transthyretin antibodies are used in several scientific applications, including:
- Western Blot (WB): To detect and quantify TTR protein levels in samples.
- Immunohistochemistry (IHC): To visualize TTR distribution in tissue sections.
- Immunocytochemistry (ICC): To study TTR localization in cultured cells.
- Enzyme-Linked Immunosorbent Assay (ELISA): To measure TTR concentrations in biological fluids .
