气候变化领域集成服务门户(CCPortal): A circulating, disease-specific, mechanism-linked biomarker for ATTR polyneuropathy diagnosis and response to therapy prediction

CCPortal

DOI	10.1073/pnas.2016072118
	A circulating, disease-specific, mechanism-linked biomarker for ATTR polyneuropathy diagnosis and response to therapy prediction
	Jiang X.; Labaudinière R.; Buxbaum J.N.; Monteiro C.; Novais M.; Coelho T.; Kelly J.W.
发表日期	2021
ISSN	00278424
卷号	118 期号:9
英文摘要	The transthyretin (TTR) amyloidoses (ATTR) are progressive, degenerative diseases resulting from dissociation of the TTR tetramer to monomers, which subsequently misfold and aggregate, forming a spectrum of aggregate structures including oligomers and amyloid fibrils. To determine whether circulating nonnative TTR (NNTTR) levels correlate with the clinical status of patients with V30M TTR familial amyloid polyneuropathy (FAP), we quantified plasma NNTTR using a newly developed sandwich enzyme-linked immunosorbent assay. The assay detected significant plasma levels of NNTTR in most presymptomatic V30M TTR carriers and in all FAP patients. NNTTR was not detected in age-matched control plasmas or in subjects with other peripheral neuropathies, suggesting NNTTR can be useful in diagnosing FAP. NNTTR levels were substantially reduced in patients receiving approved FAP disease-modifying therapies (e.g., the TTR stabilizer tafamidis, 20 mg once daily). This NNTTR decrease was seen in both the responders (average reduction 56.4 ± 4.2%; n = 49) and nonresponders (average reduction of 63.3 ± 4.8%; n = 32) at 12 mo posttreatment. Notably, high pretreatment NNTTR levels were associated with a significantly lower likelihood of clinical response to tafamidis. Our data suggest that NNTTR is a disease driver whose reduction is sufficient to ameliorate FAP so long as pretreatment NNTTR levels are below a critical clinical threshold. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Biomarker; Early diagnosis; NNTTR; Response to therapy
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180472
作者单位	Research Division, Protego Biopharma, Inc., San Diego, CA 92121, United States; Department of Molecular Medicine, Scripps Research Institute, San Diego, CA 92037, United States; Department of Chemistry, Scripps Research Institute, San Diego, CA 92037, United States; Unidade Corino de Andrade, Centro Hospitalar do Porto, Porto, 4099-001, Portugal; Department of Neurophysiology, Centro Hospitalar do Porto, Porto, 4099-001, Portugal; Skaggs Institute for Chemical Biology, Scripps Research Institute, San Diego, CA 92037, United States
推荐引用方式 GB/T 7714	Jiang X.,Labaudinière R.,Buxbaum J.N.,et al. A circulating, disease-specific, mechanism-linked biomarker for ATTR polyneuropathy diagnosis and response to therapy prediction[J],2021,118(9).
APA	Jiang X..,Labaudinière R..,Buxbaum J.N..,Monteiro C..,Novais M..,...&Kelly J.W..(2021).A circulating, disease-specific, mechanism-linked biomarker for ATTR polyneuropathy diagnosis and response to therapy prediction.Proceedings of the National Academy of Sciences of the United States of America,118(9).
MLA	Jiang X.,et al."A circulating, disease-specific, mechanism-linked biomarker for ATTR polyneuropathy diagnosis and response to therapy prediction".Proceedings of the National Academy of Sciences of the United States of America 118.9(2021).