Familial amyloidosis medical therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Roukoz A. Karam, M.D.[2]
Overview
The optimal therapy for familial amyloidosis is preventing further organ damage and correcting the effects of organ failure. The mainstay of treatment for TTR amyloidosis is liver transplant. We may also use tafamidis, patisiran, Inoteresen, diflunisal, and epigallocathechin-3-gallate.
Medical Therapy
- The mainstay of treatment for familial amyloidosis is removal of the source of abnormal TTR production.
- Since the liver is the dominant source of transthyretin, liver transplant is considered in patients with less advanced disease.
- Patients with severe cardiac complications may benefit from a heart transplant.
- Newer therapies have been studied and assessed in clinical trials. These therapies may slow or halt progression of familial ATTR amyloidosis.
- Tafamidis
- 2-(3,5–dichloro–phenyl)-benzox-azole-6-carboxylic acid is an orally administered drug that acts to stabilize the TTR tetramer through its affinity for the T4-binding site, and it does not carry the risks associated with nonsteroidal anti-inflammatory drug use.[1]
- Recently approved for familial amyloid polyneuropathy (FAP) in Europe.[2]
- This agent is being tested in ongoing trials for other forms of ATTR.
- Patisiran and Inoteresen
- TTR gene silencers.
- FDA recently approved their use for ATTRm amyloidosis with peripheral neuropathy.[3]
- Diflunisal
- Nonsteroidal anti-inflammatory drug that stabilizes tetrameric TTR in vitro by binding via the thyroid hormone receptor sites.
- Epigallocathechin-3-gallate[4]
- The most abundant catechin in green tea.
- Recent in vitro experiments show that 50μmol/l epigallocatechin-3-gallate efficiently inhibits fibril formation from amyloid β-protein, α-synucleine, and TTR.
- Converts existing fibrils into nonfibril conformers.
- Tafamidis
- Genetic counseling is recommended for individuals with hereditary amyloidosis and their family members.
References
- ↑ Bulawa CE, Connelly S, Devit M, Wang L, Weigel C, Fleming JA; et al. (2012). "Tafamidis, a potent and selective transthyretin kinetic stabilizer that inhibits the amyloid cascade". Proc Natl Acad Sci U S A. 109 (24): 9629–34. doi:10.1073/pnas.1121005109. PMC 3386102. PMID 22645360.
- ↑ Maurer MS, Schwartz JH, Gundapaneni B, Elliott PM, Merlini G, Waddington-Cruz M; et al. (2018). "Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy". N Engl J Med. 379 (11): 1007–1016. doi:10.1056/NEJMoa1805689. PMID 30145929.
- ↑ Benson MD, Waddington-Cruz M, Berk JL, Polydefkis M, Dyck PJ, Wang AK; et al. (2018). "Inotersen Treatment for Patients with Hereditary Transthyretin Amyloidosis". N Engl J Med. 379 (1): 22–31. doi:10.1056/NEJMoa1716793. PMID 29972757.
- ↑ Ferreira N, Cardoso I, Domingues MR, Vitorino R, Bastos M, Bai G; et al. (2009). "Binding of epigallocatechin-3-gallate to transthyretin modulates its amyloidogenicity". FEBS Lett. 583 (22): 3569–76. doi:10.1016/j.febslet.2009.10.062. PMID 19861125.