Familial amyloidosis medical therapy: Difference between revisions
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==Overview== | ==Overview== | ||
The optimal therapy for familial amyloidosis is | The optimal therapy for familial amyloidosis is preventing further [[Organ (anatomy)|organ]] damage and correcting the effects of [[organ failure]]. The mainstay of treatment for [[Transthyretin amyloidosis|TTR amyloidosis]] is [[Liver transplantation|liver transplant]]. We may also use [[tafamidis]], [[patisiran]], Inoteresen, [[diflunisal]], and epigallocathechin-3-gallate. | ||
==Medical Therapy== | ==Medical Therapy== | ||
*The mainstay of treatment for familial amyloidosis is removal of the source of [[abnormal]] | *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]]. | **Since the [[liver]] is the dominant source of [[transthyretin]], liver transplant is considered in [[patients]] with less advanced [[disease]]. | ||
**Patients with severe [[Heart|cardiac]] complications may benefit from a [[heart transplant]]. | **Patients with severe [[Heart|cardiac]] complications may benefit from a [[heart transplant]]. | ||
*Newer therapies have been | *Newer therapies have been studied and assessed in [[clinical trials]]. These [[Therapy|therapies]] may slow or halt progression of familial ATTR [[amyloidosis]]. | ||
**Tafamidis | **[[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.<ref name="pmid22645360">{{cite journal| author=Bulawa CE, Connelly S, Devit M, Wang L, Weigel C, Fleming JA et al.| title=Tafamidis, a potent and selective transthyretin kinetic stabilizer that inhibits the amyloid cascade. | journal=Proc Natl Acad Sci U S A | year= 2012 | volume= 109 | issue= 24 | pages= 9629-34 | pmid=22645360 | doi=10.1073/pnas.1121005109 | pmc=3386102 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22645360 }}</ref> | ***2-(3,5–dichloro–phenyl)-benzox-azole-6-carboxylic acid is an orally administered [[drug]] that acts to [[Stabilizer|stabilize]] the TTR tetramer through its affinity for the T4-binding site, and it does not carry the [[risks]] associated with [[Nonsteroidal anti-inflammatory drugs|nonsteroidal anti-inflammatory]] drug use.<ref name="pmid22645360">{{cite journal| author=Bulawa CE, Connelly S, Devit M, Wang L, Weigel C, Fleming JA et al.| title=Tafamidis, a potent and selective transthyretin kinetic stabilizer that inhibits the amyloid cascade. | journal=Proc Natl Acad Sci U S A | year= 2012 | volume= 109 | issue= 24 | pages= 9629-34 | pmid=22645360 | doi=10.1073/pnas.1121005109 | pmc=3386102 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22645360 }}</ref> | ||
***Recently approved for familial amyloid polyneuropathy (FAP) in Europe.<ref name="pmid301459292">{{cite journal| author=Maurer MS, Schwartz JH, Gundapaneni B, Elliott PM, Merlini G, Waddington-Cruz M et al.| title=Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy. | journal=N Engl J Med | year= 2018 | volume= 379 | issue= 11 | pages= 1007-1016 | pmid=30145929 | doi=10.1056/NEJMoa1805689 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30145929 }}</ref> | ***Recently approved for [[familial amyloid polyneuropathy]] (FAP) in Europe.<ref name="pmid301459292">{{cite journal| author=Maurer MS, Schwartz JH, Gundapaneni B, Elliott PM, Merlini G, Waddington-Cruz M et al.| title=Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy. | journal=N Engl J Med | year= 2018 | volume= 379 | issue= 11 | pages= 1007-1016 | pmid=30145929 | doi=10.1056/NEJMoa1805689 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30145929 }}</ref> | ||
***This agent is being tested in ongoing trials for other forms of ATTR. | ***This agent is being tested in ongoing trials for other forms of ATTR. | ||
**Patisiran and Inoteresen | **[[Patisiran]] and Inoteresen | ||
*** | ***TTR gene silencers. | ||
**Diflunisal | ***FDA recently approved their use for ATTRm amyloidosis with peripheral neuropathy.<ref name="pmid29972757">{{cite journal| author=Benson MD, Waddington-Cruz M, Berk JL, Polydefkis M, Dyck PJ, Wang AK et al.| title=Inotersen Treatment for Patients with Hereditary Transthyretin Amyloidosis. | journal=N Engl J Med | year= 2018 | volume= 379 | issue= 1 | pages= 22-31 | pmid=29972757 | doi=10.1056/NEJMoa1716793 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29972757 }}</ref> | ||
***Nonsteroidal anti-inflammatory drug that stabilizes tetrameric TTR | **[[Diflunisal]] | ||
***[[Nonsteroidal anti-inflammatory drugs|Nonsteroidal anti-inflammatory drug]] that stabilizes tetrameric TTR [[in vitro]] by binding via the [[Thyroid hormone receptor|thyroid hormone receptor sites.]] | |||
**Epigallocathechin-3-gallate<ref name="pmid19861125">{{cite journal| author=Ferreira N, Cardoso I, Domingues MR, Vitorino R, Bastos M, Bai G et al.| title=Binding of epigallocatechin-3-gallate to transthyretin modulates its amyloidogenicity. | journal=FEBS Lett | year= 2009 | volume= 583 | issue= 22 | pages= 3569-76 | pmid=19861125 | doi=10.1016/j.febslet.2009.10.062 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19861125 }}</ref> | **Epigallocathechin-3-gallate<ref name="pmid19861125">{{cite journal| author=Ferreira N, Cardoso I, Domingues MR, Vitorino R, Bastos M, Bai G et al.| title=Binding of epigallocatechin-3-gallate to transthyretin modulates its amyloidogenicity. | journal=FEBS Lett | year= 2009 | volume= 583 | issue= 22 | pages= 3569-76 | pmid=19861125 | doi=10.1016/j.febslet.2009.10.062 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19861125 }}</ref> | ||
***Recent in vitro experiments show that 50μmol/l epigallocatechin-3-gallate | ***The most abundant [[catechin]] in [[green tea]]. | ||
***Recent [[In vitro fertilization|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. <br /> | ***Converts existing fibrils into nonfibril conformers. <br /> | ||
*Genetic counseling is recommended for individuals with hereditary amyloidosis and their family members. | *Genetic counseling is recommended for individuals with hereditary amyloidosis and their family members. | ||
Latest revision as of 19:04, 25 November 2019
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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.