Emerging treatments for amyloidosis

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Emerging treatments for amyloidosis Rabya H. Sayed, Philip N. Hawkins, Helen J. Lachmann Kidney International Volume 87, Issue 3, Pages 516-526 (March 2015) DOI: 10.1038/ki.2014.368 Copyright © 2015 International Society of Nephrology Terms and Conditions

Figure 1 Sections of a renal biopsy sample were stained with Congo red dye and viewed at × 200 magnification. (a) Amorphous deposits of eosinophilic material are visible within the glomerulus. (b) Pathognomonic green birefringence of amyloid deposits is visible when viewed under cross-polarized light. (c) Immunostaining of the amyloid deposits with anti-κ antibodies was strongly positive (brown stain). Kidney International 2015 87, 516-526DOI: (10.1038/ki.2014.368) Copyright © 2015 International Society of Nephrology Terms and Conditions

Figure 2 Hepatocyte schematic demonstrating the mechanism by which small interfering RNAs (siRNAs) block the transcription process and antisense oligonucleotides interfere with the translation process, ultimately preventing transthyretin (TTR) formation. (1) The siRNAs bind to the RNA-inducing silencing complex (RISC) in an adenosine triphosphate (ATP)–dependent manner. (2) This multisubunit protein complex migrates toward messenger RNA (mRNA). At some point, the siRNA unwinds and the antisense strand remains bound to the RISC and blocks transcription by the direct degradation of the target mRNA sequence through the use of both endo- and exonucleases.37,38 (3) The mRNA migrates into the cytoplasm where (4) hybridization with the antisense oligonucleotide prevents protein translocation (5). Kidney International 2015 87, 516-526DOI: (10.1038/ki.2014.368) Copyright © 2015 International Society of Nephrology Terms and Conditions

Figure 3 Iodine-123 (123I)-labeled serum amyloid P (SAP) component scintigraphy. Anterior-posterior view of an SAP scan, demonstrating (a) a large total body amyloid load with hepatic and splenic involvement (b) with regression after nine cycles of chemotherapy, resulting in a small total body amyloid load. Kidney International 2015 87, 516-526DOI: (10.1038/ki.2014.368) Copyright © 2015 International Society of Nephrology Terms and Conditions