1、familial amyloid polyneuropathy 1. J Peripher Nerv Syst. 2015 Dec 13. doi: 10.1111/jns.12153. Epub ahead of print “Red-flag“ symptom clusters in transthyretin familial amyloid polyneuropathy. Conceio I(1), Gonzlez-Duarte A(2), Obici L(3), Schmidt HH(4), Simoneau D(5), Ong ML(6), Amass L(6). Author i
2、nformation: (1)CHLN - Hospital de Santa Maria, and Clinical and Translational Physiology Unit, Physiology Institute, Faculty of Medicine-IMM, Lisbon, Portugal. (2)Instituto Nacional de Ciencias Mdicas y Nutricin Salvador Zubirn, Mxico City, Mxico. (3)Amyloidosis Research and Treatment Center, Fondaz
3、ione IRCCS Policlinico San Matteo, Pavia, Italy. (4)Klinik fr Transplantationsmedizin, Universittsklinikum Mnster, Mnster, Germany. (5)Pfizer IO, Paris, France. (6)Pfizer Inc, New York, NY, USA. BACKGROUND: Transthyretin familial amyloid polyneuropathy (TTR-FAP) is a rare, progressive, life-threaten
4、ing, hereditary disorder caused by mutations in the transthyretin gene and characterized by extracellular deposition of transthyretin-derived amyloid fibrils in peripheral and autonomic nerves, heart, and other organs. TTR-FAP is frequently diagnosed late because the disease is difficult to recogniz
5、e due to phenotypic heterogeneity. METHODS: Based on published literature and expert opinion, symptom clusters suggesting TTR-FAP are reviewed, and practical guidance to facilitate earlier diagnosis is provided. Results and conclusions TTR-FAP should be suspected if progressive peripheral sensory-mo
6、tor neuropathy is observed in combination with one or more of the following: family history of a neuropathy, autonomic dysfunction, cardiac hypertrophy, gastrointestinal problems, inexplicable weight loss, carpal tunnel syndrome, renal impairment, or ocular involvement. If TTR-FAP is suspected, tran
7、sthyretin genotyping, confirmation of amyloid in tissue biopsy, large- and small-fiber assessment by nerve conduction studies and autonomic system evaluations, and cardiac testing should be performed. This article is protected by copyright. All rights reserved. PMID: 26663427 PubMed - as supplied by
8、 publisher 2. Transplantation. 2015 Dec 11. Epub ahead of print Survival After Transplantation in Patients With Mutations Other Than Val30Met: Extracts From the FAP World Transplant Registry. Suhr OB(1), Larsson M, Ericzon BG, Wilczek HE; FAPWTRs investigators. Author information: (1)1 Department of
9、 Public Health and Clinical Medicine, Ume University Hospital, Ume, Sweden. 2 Division of Transplantation Surgery, Karolinska Institutet, CLINTEC, Karolinska University Hospital, Huddinge, Stockholm, Sweden. BACKGROUND: Liver transplantation (LTx) has been performed for hereditary transthyretin amyl
10、oidosis (ATTR) since 1990. Outcomes for a relatively large series of LTx ATTR patients with the Val30Met (mutation are available, but for non-Val30Met patients, only a few reports with a small number of patients exist. Here, we present outcomes for non-Val30Met ATTR patients after LTx, as reported t
11、o the Familial Amyloid Polyneuropathy World Transplant Registry (FAPWTR). METHODS: Data regarding outcome were extracted for all non-Val30Met patients reported to the registry. Survival rates were analyzed by the Kaplan-Meier method and log-rank test. RESULTS: The total number of patients with a non
12、-Val30Met mutation in the registry was 264 (174 men and 90 women), representing 57 mutations. The 10-year survival varied markedly for the 9 most common mutations, ranging from 21% for Ser50Arg to 85% for Val71Ala. Poor survival was noted for all mutations with leptomeningeal complications except fo
13、r those with the Tyr114Cys mutation. CONCLUSIONS: Large differences in survival were observed relative to different mutations and between mutations with similar phenotypes. Excellent survival was noted for mutations, such as Leu111Met, Val71Ala, and Leu58His. Patients with mutations other than Val30
14、Met are not a homogeneous group, and the term non-Val30Met should be used with caution or avoided. Moreover, for several mutations, data are too limited to allow evaluation of the efficacy of LTx, and continuous international collaboration is important for obtaining treatment guidance.This is an ope
15、n-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. PMID: 26656838 PubMed - as sup
16、plied by publisher 3. Ann Med. 2015 Dec;47(8):625-38. doi: 10.3109/07853890.2015.1068949. Epub 2015 Nov 27. Evolving landscape in the management of transthyretin amyloidosis. Hawkins PN(1), Ando Y(2), Dispenzeri A(3), Gonzalez-Duarte A(4), Adams D(5), Suhr OB(6). Author information: (1)a National Am
17、yloidosis Centre, Royal Free Hospital, University College London , London , UK. (2)b Department of Neurology , Graduate School of Medical Sciences Kumamoto University , Kumamoto , Japan. (3)c Mayo Clinic, Division of Hematology , Rochester, Minnesota, USA. (4)d Instituto Nacional de Ciencias Mdicas
18、y Nutricin Salvador Zubirn , Mexico City , Mexico. (5)e National Reference Centre for FAP, APHP, CHU Bictre, Universit Paris-Sud, INSERM U788 , Paris , France. (6)f Department of Public Health and Clinical Medicine , Ume University , Ume , Sweden. Transthyretin (TTR) amyloidosis (ATTR amyloidosis) i
19、s a multisystemic, multigenotypic disease resulting from deposition of insoluble ATTR amyloid fibrils in various organs and tissues. Although considered rare, the prevalence of this serious disease is likely underestimated because symptoms can be non-specific and diagnosis largely relies on amyloid
20、detection in tissue biopsies. Treatment is guided by which tissues/organs are involved, although therapeutic options are limited for patients with late-stage disease. Indeed, enthusiasm for liver transplantation for familial ATTR amyloidosis with polyneuropathy was dampened by poor outcomes among pa
21、tients with significant neurological deficits or cardiac involvement. Hence, there remains an unmet medical need for new therapies. The TTR stabilizers tafamidis and diflunisal slow disease progression in some patients with ATTR amyloidosis with polyneuropathy, and the postulated synergistic effect
22、of doxycycline and tauroursodeoxycholic acid on dissolution of amyloid is under investigation. Another therapeutic approach is to reduce production of the amyloidogenic protein, TTR. Plasma TTR concentration can be significantly reduced with ISIS-TTRRx, an investigational antisense oligonucleotide-b
23、ased drug, or with patisiran and revusiran, which are investigational RNA interference-based therapeutics that target the liver. The evolving treatment landscape for ATTR amyloidosis brings hope for further improvements in clinical outcomes for patients with this debilitating disease. PMID: 26611723
24、 PubMed - in process 4. J Am Coll Cardiol. 2015 Dec 1;66(21):2451-66. doi: 10.1016/j.jacc.2015.09.075. Diagnosis, Prognosis, and Therapy of Transthyretin Amyloidosis. Gertz MA(1), Benson MD(2), Dyck PJ(3), Grogan M(4), Coelho T(5), Cruz M(6), Berk JL(7), Plante-Bordeneuve V(8), Schmidt HH(9), Merlin
25、i G(10). Author information: (1)Division of Hematology, Mayo Clinic, Rochester, Minnesota. Electronic address: gertz.moriemayo.edu. (2)Indiana University School of Medicine, Indianapolis, Indiana. (3)Division of Peripheral Nerve, Mayo Clinic, Rochester, Minnesota. (4)Division of Cardiovascular Disea
26、ses, Mayo Clinic, Rochester, Minnesota. (5)Hospital de Santo Antonio, Porto, Portugal. (6)Federal University of Rio de Janeiro of Brazil, University Hospital, Rio de Janeiro, Brazil. (7)Amyloidosis Center, Boston University School of Medicine, Boston, Massachusetts. (8)University Hospital, Henri Mon
27、dor, Crteil, France. (9)Universittsklinikum Mnster, Mnster, Germany. (10)Department of Molecular Medicine, University of Pavia, Pavia, Lombardy, Italy. Transthyretin amyloidosis is a fatal disorder that is characterized primarily by progressive neuropathy and cardiomyopathy. It occurs in both a muta
28、nt form (with autosomal dominant inheritance) and a wild-type form (with predominant cardiac involvement). This article guides clinicians as to when the disease should be suspected, describes the appropriate diagnostic evaluation for those with known or suspected amyloidosis, and reviews the interve
29、ntions currently available for affected patients. Copyright 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. PMID: 26610878 PubMed - in process 5. Neurol Ther. 2015 Dec;4(2):61-79. doi: 10.1007/s40120-015-0031-3. Epub 2015 Aug 15. A Review of Tafamidis
30、for the Treatment of Transthyretin-Related Amyloidosis. Waddington Cruz M(1), Benson MD(2). Author information: (1)Amyloidosis Research and Treatment Center (CEPARM), University Hospital (HUCFF), Federal University of Rio de Janeiro, Rio De Janeiro, Brazil. . (2)Department of Pathology and Laborator
31、y Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. Transthyretin (TTR)-related amyloidosis (ATTR) is a devastating disease which affects a combination of organs including the heart and the peripheral nerves, and which has a fatal outcome if not treated within a average of 10 y
32、ears. Tafamidis, or 2-(3,5-dichloro-phenyl)-benzoxazole-6-carboxylic acid, selectively binds to TTR with negative cooperativity and kinetically stabilizes wild-type native TTR and mutant TTR; tafamidis therefore has the potential to halt the amyloidogenic cascade initiated by TTR tetramer dissociati
33、on, monomer misfolding, and aggregation. The first tafamidis trial, Fx-005, evaluated the effect of 18 months of tafamidis treatment (20 mg once daily) on disease progression, as well as assessing its safety in TTR-FAP Val30Met patients. The secondary objective of this trial was to study the pharmac
34、odynamic stabilization of mutated TTR. Tafamidis proved effective in reducing the progress of neuropathy, and in maintaining the nutritional status and quality of life of stage 1 (able to walk without support) Val3OMet TTR-FAP patients. Furthermore, TTR stabilization was achieved in more than 90% of
35、 patients. An extension study, Fx-006, was conducted to determine the long-term safety and tolerability of tafamidis and to assess the efficacy of the drug on slowing disease progression. No significant safety or tolerability issues were noticed. Taken together, the results from both trials indicate
36、d that the beneficial effects of tafamidis were sustained over a 30-month period and that starting treatment early is desirable. Results are expected from an extended open-label study but data that have already been presented show that long-term use of tafamidis in Val30Met patients is associated wi
37、th reduced progression in polyneuropathy. Tafamidis was initially approved for commercial use in Europe in 2011 and has since been approved for use in Japan, Mexico, and Argentina where it is used as a first-line treatment option for patients with early-stage TTR-FAP. Patients should be carefully fo
38、llowed at referral centers to ascertain the individual response to treatment. In cases of discontinuation, liver transplantation and enrollment in clinical trials of novel drugs aimed mostly toward suppression of TTR production are options. PMCID: PMC4685869 PMID: 26662359 PubMed 6. Parkinsonism Rel
39、at Disord. 2015 Dec;21(12):1465-8. doi: 10.1016/j.parkreldis.2015.10.012. Epub 2015 Oct 21. A peripheral pathway to restless legs syndrome? Clues from familial amyloid polyneuropathy. Teodoro T(1), Viana P(2), Abreu D(3), Conceio I(4), Peralta R(5), Ferreira JJ(6). Author information: (1)Department
40、of Neurology, Hospital de Santa Maria, Lisboa, Portugal; Clinical Pharmacology Unit, Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisboa, Portugal; St Georges University London, London, United Kingdom. Electronic address: . (2)Department of Neurology, Hospital de Santa
41、 Maria, Lisboa, Portugal. (3)Clinical Pharmacology Unit, Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisboa, Portugal. (4)Department of Neurology, Hospital de Santa Maria, Lisboa, Portugal; Translational and Clinical Physiology Unit, Instituto de Medicina Molecular, F
42、aculty of Medicine, University of Lisbon, Lisboa, Portugal. (5)Department of Neurology, Hospital de Santa Maria, Lisboa, Portugal; EEG/Sleep Laboratory, Hospital de Santa Maria, Lisboa, Portugal. (6)Department of Neurology, Hospital de Santa Maria, Lisboa, Portugal; Clinical Pharmacology Unit, Insti
43、tuto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisboa, Portugal. BACKGROUND: The relationship between restless legs syndrome (RLS) and peripheral neuropathy remains unclear. In order to clarify this relationship, we investigated if RLS is increased in familial amyloid polyneu
44、ropathy related to transthyretin (TTR-FAP) and investigated factors associated with RLS in this population. METHODS: RLS frequency was compared between TTR-FAP patients and controls. Secondly, TTR-FAP patients with and without RLS were compared regarding demographic and clinical characteristics. RES
45、ULTS: RLS frequency was significantly increased in TTR-FAP, with 18/98 (18.4%) cases contrasting with 5/104 (4.8%) controls (p-value 0.002). This difference remained significant after adjusting for confounders. In TTR-FAP patients, female sex (p-value 0.037), obesity (p-value 0.036) and weight exces
46、s (p-value 0.048) were associated with RLS, contrary to other classical RLS risk factors. CONCLUSIONS: RLS frequency is increased in TTR-FAP, thus supporting an association between RLS and neuropathy. This may represent a peripheral pathway in RLS pathogenesis. Furthermore, our results suggest that
47、female sex and obesity/weight excess may be risk factors for RLS development among TTR-FAP patients. Copyright 2015 Elsevier Ltd. All rights reserved. PMID: 26508424 PubMed - in process 7. Rev Neurosci. 2015 Dec 1;26(6):691-8. doi: 10.1515/revneuro-2015-0003. Receptor for advanced glycation end-prod
48、ucts in neurodegenerative diseases. Juranek J, Ray R, Banach M, Rai V. This review, for the first time, aims to summarize the current knowledge in the emerging field of RAGE (receptor for advanced glycation end-products) studies in neurodegeneration and neurodegenerative diseases. RAGE, a member of
49、the multiligand cell surface immunoglobulin family, has been implicated in numerous pathological conditions - from diabetes and cardiovascular diseases to tumors and neurodegenerative disorders, such as Alzheimers disease, familial amyloid polyneuropathy, diabetic neuropathy, Parkinsons disease, and Huntingtons disease. Until now, the detailed mechanisms of the contribution of RAGE to neurodegeneration remain elusive; however, mounting evidence suggests that its detr
