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CC BY 4.0 · Arq Neuropsiquiatr 2025; 83(07): s00451809401
DOI: 10.1055/s-0045-1809401
History of Neurology

40 years of CEPARM: transforming amyloidosis related to transthyretin from neglect to recognition

Marcia Waddington Cruz 
1   Universidade Federal do Rio de Janeiro, Faculdade de Medicina, Programa de Pós-Graduação em Clínica Médica, Rio de Janeiro RJ, Brazil.
,
Marleide da Mota Gomes 
2   Universidade Federal do Rio de Janeiro, Instituto de Neurologia, Rio de Janeiro RJ, Brazil.
3   Universidade Federal do Rio de Janeiro, Instituto de Psiquiatria, Laboratório de História da Psiquiatria, Neurologia e Saúde Mental, Rio de Janeiro RJ, Brazil.
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Abstract

Variant transthyretin amyloidosis with polyneuropathy (ATTRv-PN) and cardiomyopathy (ATTRv-CM), formerly known as familial amyloidotic polyneuropathy (FAP), is a severe, progressive disorder caused by mutations in the transthyretin (TTR) gene. Historically, FAP was considered a neglected disease due to its rarity and the limited understanding of its pathophysiology, which led to minimal research funding and few therapeutic options. The present article explores the transformative role of Centro de Paramiloidose Antônio Rodrigues de Mello (CEPARM), established in 1984, in elevating the status of FAP through significant advancements in research and treatment. Although CEPARM was not the sole catalyst for this shift, its contributions in liver transplantation, the development of pharmacological therapies, and holistic patient care have substantially improved the recognition and management of FAP. The article also examines CEPARM's impact on patient care, the ongoing challenges, and ethical considerations within the field.

Keywords

Amyloid Neuropathies, Familial - Prealbumin - Polyneuropathies - Cardiomyopathies - Liver Transplantation - Drug Therapy

Authors' Contributions

Conceptualization: MMG, MWC; Writing - review & editing: MMG, MWC.


Data Availability Statement

The contents are already available within the present article.


Editor-in-Chief: Hélio A. G. Teive 0000-0003-2305-1073.


Associate Editor: Eliasz Engelhardt 0000-0003-4168-1992.




Publication History

Received: 19 November 2024

Accepted: 03 April 2025

Article published online:
20 June 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/)

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Bibliographical Record
Marcia Waddington Cruz, Marleide da Mota Gomes. 40 years of CEPARM: transforming amyloidosis related to transthyretin from neglect to recognition. Arq Neuropsiquiatr 2025; 83: s00451809401.
DOI: 10.1055/s-0045-1809401
 

  • References

  • 1 Adams D, Sekijima Y, Conceição I, Waddington-Cruz M, Polydefkis M, Echaniz-Laguna A, Reilly MM. Hereditary transthyretin amyloid neuropathies: advances in pathophysiology, biomarkers, and treatment. Lancet Neurol 2023; 22 (11) 1061-1074
    CrossrefPubMedSearch in Google Scholar
  • 2 Buxbaum JN, Eisenberg DS, Fändrich M, McPhail ED, Merlini G, Saraiva MJM. et al. Amyloid nomenclature 2024: update, novel proteins, and recommendations by the International Society of Amyloidosis (ISA) Nomenclature Committee. Amyloid 2024; 31 (04) 249-256
    CrossrefPubMedSearch in Google Scholar
  • 3 Brooks PJ, Grady AC, Groft S, Ho L, Lumsden J, Shah M. et al. The division of rare diseases research innovation at the national center for advancing translational sciences, NIH: mission, history, and current research activities. Rare Dis Orphan Drug J 2024; 3 (02) 15
    CrossrefSearch in Google Scholar
  • 4 Hindhede AL, Larsen K. Prestige hierarchies of diseases and specialities in a field perspective. Soc Theory Health 2019; 17 (02) 213-230
    CrossrefSearch in Google Scholar
  • 5 Koike H, Misu K-i, Ikeda S-i, Ando Y, Nakazato M, Ando E. et al; Study Group for Hereditary Neuropathy in Japan. Type I (transthyretin Met30) familial amyloid polyneuropathy in Japan: early- vs late-onset form. Arch Neurol 2002; 59 (11) 1771-1776
    CrossrefPubMedSearch in Google Scholar
  • 6 Pinto MV, Pinto LF, Dias M, Rosa RS, Mundayat R, Pedrosa RC, Waddington-Cruz M. Late-onset hereditary ATTR V30M amyloidosis with polyneuropathy: Characterization of Brazilian subjects from the THAOS registry. J Neurol Sci 2019; 403: 1-6
    CrossrefPubMedSearch in Google Scholar
  • 7 Gomes MdM, Cruz MW. Homage to Paula Coutinho – a pioneer in portuguese and worldwide neurogenetics. Rev Bras Neurol 2022; 58 (04) 30-33 . Available from: https://neuro.org.br/pdfs/RBN-58/RBN-584-DEZEMBRO/RBN-584-DEZEMBRO-30-33.pdf
    Search in Google Scholar
  • 8 Gomes MM. Amiloidose familiar por transtirretina TTR Val30Met e os primórdios do Centro de Estudos de Paramiloidose / Principles of the Familial transthyretin amyloidosis TTR Val30Met and the beginning of the Paramyloidosis Center of Antonio Rodrigues de Mello. Rev Bras Neurol 2011; 47 (02) 7-21
    Search in Google Scholar
  • 9 CEPARM. Rev Bras Neurol 1985; 21 (02) 74
  • 10 Cruz MW, Pinto MV, Pinto LF, Gervais R, Dias M, Perez C. et al. Baseline disease characteristics in Brazilian patients enrolled in Transthyretin Amyloidosis Outcome Survey (THAOS). Arq Neuropsiquiatr 2019; 77 (02) 96-100
    CrossrefSearch in Google Scholar
  • 11 Waddington-Cruz M, Pinto MV, Foguel D. Geographic distribution of ATTR cases from CEPARM across the Brazilian territory and their clinical aspects, demographics, ethnical and family background. Amyloid 2019; 26: 53-54
    CrossrefPubMedSearch in Google Scholar
  • 12 Ericzon BG, Wilczek HE, Larsson M, Wijayatunga P, Stangou A, Pena JR. et al. Liver Transplantation for Hereditary Transthyretin Amyloidosis: After 20 Years Still the Best Therapeutic Alternative?. Transplantation 2015; 99 (09) 1847-1854
    CrossrefPubMedSearch in Google Scholar
  • 13 Coelho T, Maia LF, Silva AMd, Cruz MW, Planté-Bordeneuve V, Lozeron P. et al. Tafamidis for transthyretin familial amyloid polyneuropathy: a randomized, controlled trial. Neurology 2012; 79 (08) 785-792
    CrossrefPubMedSearch in Google Scholar
  • 14 Maurer MS, Schwartz JH, Gundapaneni B, Elliott PM, Merlini G, Waddington-Cruz M. et al; ATTR-ACT Study Investigators. Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy. N Engl J Med 2018; 379 (11) 1007-1016
    CrossrefPubMedSearch in Google Scholar
  • 15 Adams D, Polydefkis M, González-Duarte A, Wixner J, Kristen AV, Schmidt HH. et al; patisiran Global OLE study group. Long-term safety and efficacy of patisiran for hereditary transthyretin-mediated amyloidosis with polyneuropathy: 12-month results of an open-label extension study. Lancet Neurol 2021; 20 (01) 49-59
    CrossrefSearch in Google Scholar
  • 16 Benson MD, Waddington-Cruz M, Berk JL, Polydefkis M, Dyck PJ, Wang AK. et al. Inotersen Treatment for Patients with Hereditary Transthyretin Amyloidosis. N Engl J Med 2018; 379 (01) 22-31
    CrossrefPubMedSearch in Google Scholar
  • 17 Adams D, Tournev IL, Taylor MS, Coelho T, Planté-Bordeneuve V, Berk JL. et al; HELIOS-A Collaborators. Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: a randomized clinical trial. Amyloid 2023; 30 (01) 1-9
    CrossrefPubMedSearch in Google Scholar
  • 18 Coelho T, Marques Jr W, Dasgupta NR, Chao C-C, Parman Y, França Jr MC. et al; NEURO-TTRansform Investigators. Eplontersen for Hereditary Transthyretin Amyloidosis With Polyneuropathy. JAMA 2023; 330 (15) 1448-1458
    CrossrefPubMedSearch in Google Scholar
  • 19 Dias M, Pinto LF, Pinto MV, Gervais R, Accioli P, Amorim G. et al. Real-life experience with inotersen at CEPARM, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro. Arq Neuropsiquiatr 2024; 82 (04) 1-7
    Thieme ConnectPubMedSearch in Google Scholar
  • 20 Pinto MV, França Jr MC, Gonçalves MVM, Machado-Costa MC, Freitas MRGd, Gondim FdAA. et al. Brazilian consensus for diagnosis, management and treatment of hereditary transthyretin amyloidosis with peripheral neuropathy: second edition. Arq Neuropsiquiatr 2023; 81 (03) 308-321
    Thieme ConnectPubMedSearch in Google Scholar