Generic placeholder image

Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Unfolding Cardiac Amyloidosis –From Pathophysiology to Cure

Author(s): Klemens Ablasser, Nicolas Verheyen, Theresa Glantschnig, Giulio Agnetti and Peter P. Rainer*

Volume 26, Issue 16, 2019

Page: [2865 - 2878] Pages: 14

DOI: 10.2174/0929867325666180104153338

Price: $65


Deposition of amyloidogenic proteins leading to the formation of amyloid fibrils in the myocardium causes cardiac amyloidosis. Although any form of systemic amyloidosis can affect the heart, light-chain (AL) or transthyretin amyloidosis (ATTR) account for the majority of diagnosed cardiac amyloid deposition. The extent of cardiac disease independently predicts mortality. Thus, the reversal of arrest of adverse cardiac remodeling is the target of current therapies. Here, we provide a condensed overview on the pathophysiology of AL and ATTR cardiac amyloidoses and describe treatments that are currently used or investigated in clinical or preclinical trials. We also briefly discuss acquired amyloid deposition in cardiovascular disease other than AL or ATTR.

Keywords: Amyloidosis, heart failure, pre-amyloid oligomers, fibrils, immunoglobulin light chains, transthyretin, desmin, posttranslational modification.

Quarta, C.C.; Solomon, S.D.; Uraizee, I.; Kruger, J.; Longhi, S.; Ferlito, M.; Gagliardi, C.; Milandri, A.; Rapezzi, C.; Falk, R.H. Left ventricular structure and function in transthyretin-related versus light-chain cardiac amyloidosis. Circulation, 2014, 129(18), 1840-1849. []. [PMID: 24563469].
Bodez, D.; Ternacle, J.; Guellich, A.; Galat, A.; Lim, P.; Radu, C.; Guendouz, S.; Bergoend, E.; Couetil, J.P.; Hittinger, L.; Dubois-Randé, J.L.; Plante-Bordeneuve, V.; Deux, J.F.; Mohty, D.; Damy, T. Prognostic value of right ventricular systolic function in cardiac amyloidosis. Amyloid, 2016, 23(3), 158-167. []. [PMID: 27348696].
Phelan, D.; Collier, P.; Thavendiranathan, P.; Popović, Z.B.; Hanna, M.; Plana, J.C.; Marwick, T.H.; Thomas, J.D. Relative apical sparing of longitudinal strain using two-dimensional speckle-tracking echocardiography is both sensitive and specific for the diagnosis of cardiac amyloidosis. Heart, 2012, 98(19), 1442-1448. []. [PMID: 22865865].
Bostan, C.; Sinan, U.Y.; Canbolat, P.; Kucukoglu, S. Cardiac amyloidosis cases with relative apical sparing of longitudinal strain. Echocardiography, 2014, 31(2), 241-244. []. [PMID: 24304289].
Connors, L.H.; Sam, F.; Skinner, M.; Salinaro, F.; Sun, F.; Ruberg, F.L.; Berk, J.L.; Seldin, D.C. Heart failure resulting from age-related cardiac amyloid disease associated with wild-type transthyretin: a prospective, observational cohort study. Circulation, 2016, 133(3), 282-290. []. [PMID: 26660282].
Bennani Smires, Y.; Victor, G.; Ribes, D.; Berry, M.; Cognet, T.; Méjean, S.; Huart, A.; Roussel, M.; Petermann, A.; Roncalli, J.; Carrié, D.; Rousseau, H.; Berry, I.; Chauveau, D.; Galinier, M.; Lairez, O. Pilot study for left ventricular imaging phenotype of patients over 65 years old with heart failure and preserved ejection fraction: the high prevalence of amyloid cardiomyopathy. Int. J. Cardiovasc. Imaging, 2016, 32(9), 1403-1413. []. [PMID: 27240600].
Kumar, S.; Dispenzieri, A.; Lacy, M.Q.; Hayman, S.R.; Buadi, F.K.; Colby, C.; Laumann, K.; Zeldenrust, S.R.; Leung, N.; Dingli, D.; Greipp, P.R.; Lust, J.A.; Russell, S.J.; Kyle, R.A.; Rajkumar, S.V.; Gertz, M.A. Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements. J. Clin. Oncol., 2012, 30(9), 989-995. []. [PMID: 22331953].
Pinney, J.H.; Smith, C.J.; Taube, J.B.; Lachmann, H.J.; Venner, C.P.; Gibbs, S.D.; Dungu, J.; Banypersad, S.M.; Wechalekar, A.D.; Whelan, C.J.; Hawkins, P.N.; Gillmore, J.D. Systemic amyloidosis in England: an epidemiological study. Br. J. Haematol., 2013, 161(4), 525-532. []. [PMID: 23480608].
Kyle, R.A.; Linos, A.; Beard, C.M.; Linke, R.P.; Gertz, M.A.; O’Fallon, W.M.; Kurland, L.T. Incidence and natural history of primary systemic amyloidosis in Olmsted County, Minnesota, 1950 through 1989. Blood, 1992, 79(7), 1817-1822. [PMID: 1558973].
Seo, S.R.; Jang, S.Y.; Lee, G.Y.; Choi, B.; Chun, H.; Cho, E.J.; Cho, S.I. Prevalence of amyloidosis in Korea. Orphanet J. Rare Dis., 2017, 12(1), 152. []. [PMID: 28877709].
Wechalekar, A.D.; Gillmore, J.D.; Hawkins, P.N. Systemic amyloidosis. Lancet, 2016, 387(10038), 2641-2654. []. [PMID: 26719234].
Tanskanen, M.; Peuralinna, T.; Polvikoski, T.; Notkola, I.L.; Sulkava, R.; Hardy, J.; Singleton, A.; Kiuru-Enari, S.; Paetau, A.; Tienari, P.J.; Myllykangas, L. Senile systemic amyloidosis affects 25% of the very aged and associates with genetic variation in alpha2-macroglobulin and tau: a population-based autopsy study. Ann. Med., 2008, 40(3), 232-239. []. [PMID: 18382889].
Milani, P.; Basset, M.; Russo, F.; Foli, A.; Merlini, G.; Palladini, G. Patients with light-chain amyloidosis and low free light-chain burden have distinct clinical features and outcome. Blood, 2017, 130(5), 625-631. []. [PMID: 28546143].
Gertz, M.A.; Benson, M.D.; Dyck, P.J.; Grogan, M.; Coelho, T.; Cruz, M.; Berk, J.L.; Plante-Bordeneuve, V.; Schmidt, H.H.; Merlini, G. Diagnosis, prognosis, and therapy of transthyretin amyloidosis. J. Am. Coll. Cardiol., 2015, 66(21), 2451-2466. []. [PMID: 26610878].
Buxbaum, J.N.; Ruberg, F.L. Transthyretin V122I (pV142I)* cardiac amyloidosis: an age-dependent autosomal dominant cardiomyopathy too common to be overlooked as a cause of significant heart disease in elderly African Americans. Genet. Med., 2017, 19(7), 733-742. []. [PMID: 28102864].
Dungu, J.N.; Papadopoulou, S.A.; Wykes, K.; Mahmood, I.; Marshall, J.; Valencia, O.; Fontana, M.; Whelan, C.J.; Gillmore, J.D.; Hawkins, P.N.; Anderson, L.J. Afro-caribbean heart failure in the United Kingdom: Cause, outcomes, and ATTR V122I cardiac amyloidosis. Circ Heart Fail, 2016, 9(9)e003352 []. [PMID: 27618855].
Jacobson, D.R.; Alexander, A.A.; Tagoe, C.; Buxbaum, J.N. Prevalence of the amyloidogenic transthyretin (TTR) V122I allele in 14 333 African-Americans. Amyloid, 2015, 22(3), 171-174. []. [PMID: 26123279].
González-López, E.; Gallego-Delgado, M.; Guzzo-Merello, G.; de Haro-Del Moral, F.J.; Cobo-Marcos, M.; Robles, C.; Bornstein, B.; Salas, C.; Lara-Pezzi, E.; Alonso-Pulpon, L.; Garcia-Pavia, P. Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejection fraction. Eur. Heart J., 2015, 36(38), 2585-2594. []. [PMID: 26224076].
Pinney, J.H.; Whelan, C.J.; Petrie, A.; Dungu, J.; Banypersad, S.M.; Sattianayagam, P.; Wechalekar, A.; Gibbs, S.D.; Venner, C.P.; Wassef, N.; McCarthy, C.A.; Gilbertson, J.A.; Rowczenio, D.; Hawkins, P.N.; Gillmore, J.D.; Lachmann, H.J. Senile systemic amyloidosis: clinical features at presentation and outcome. J. Am. Heart Assoc., 2013, 2(2)e000098 []. [PMID: 23608605].
Kyle, R.A.; Spittell, P.C.; Gertz, M.A.; Li, C.Y.; Edwards, W.D.; Olson, L.J.; Thibodeau, S.N. The premortem recognition of systemic senile amyloidosis with cardiac involvement. Am. J. Med., 1996, 101(4), 395-400. []. [PMID: 8873510].
Ruberg, F.L.; Maurer, M.S.; Judge, D.P.; Zeldenrust, S.; Skinner, M.; Kim, A.Y.; Falk, R.H.; Cheung, K.N.; Patel, A.R.; Pano, A.; Packman, J.; Grogan, D.R. Prospective evaluation of the morbidity and mortality of wild-type and V122I mutant transthyretin amyloid cardiomy-opathy: the Transthyretin Amyloidosis Cardiac Study (TRACS) Am Heart J,, 2012, 164(2), 222, 228. e1.
Esplin, B.L.; Gertz, M.A. Current trends in diagnosis and management of cardiac amyloidosis. Curr. Probl. Cardiol., 2013, 38(2), 53-96. []. [PMID: 23337445].
Merlini, G.; Bellotti, V. Molecular mechanisms of amyloidosis. N. Engl. J. Med., 2003, 349(6), 583-596. []. [PMID: 12904524].
Tennent, G.A.; Lovat, L.B.; Pepys, M.B. Serum amyloid P component prevents proteolysis of the amyloid fibrils of Alzheimer disease and systemic amyloidosis. Proc. Natl. Acad. Sci. USA, 1995, 92(10), 4299-4303. []. [PMID: 7753801].
Ng, B.; Connors, L.H.; Davidoff, R.; Skinner, M.; Falk, R.H. Senile systemic amyloidosis presenting with heart failure: a comparison with light chain-associated amyloidosis. Arch. Intern. Med., 2005, 165(12), 1425-1429. []. [PMID: 15983293].
Bhat, A.; Selmi, C.; Naguwa, S.M.; Cheema, G.S.; Gershwin, M.E. Currents concepts on the immunopathology of amyloidosis. Clin. Rev. Allergy Immunol., 2010, 38(2-3), 97-106. []. [PMID: 19626465].
Gertz, M.A. Immunoglobulin light chain amyloidosis: 2014 update on diagnosis, prognosis, and treatment. Am. J. Hematol., 2014, 89(12), 1132-1140. []. [PMID: 25407896].
Marin-Argany, M.; Lin, Y.; Misra, P.; Williams, A.; Wall, J.S.; Howell, K.G.; Elsbernd, L.R.; McClure, M.; Ramirez-Alvarado, M. Cell damage in light chain amyloidosis: Fibril internalization, toxicity and cell-mediated seeding. J. Biol. Chem., 2016, 291(38), 19813-19825. []. [PMID: 27462073].
Dispenzieri, A.; Lacy, M.Q.; Katzmann, J.A.; Rajkumar, S.V.; Abraham, R.S.; Hayman, S.R.; Kumar, S.K.; Clark, R.; Kyle, R.A.; Litzow, M.R.; Inwards, D.J.; Ansell, S.M.; Micallef, I.M.; Porrata, L.F.; Elliott, M.A.; Johnston, P.B.; Greipp, P.R.; Witzig, T.E.; Zeldenrust, S.R.; Russell, S.J.; Gastineau, D.; Gertz, M.A. Absolute values of immunoglobulin free light chains are prognostic in patients with primary systemic amyloidosis undergoing peripheral blood stem cell transplantation. Blood, 2006, 107(8), 3378-3383. []. [PMID: 16397135].
Madan, S.; Kumar, S.K.; Dispenzieri, A.; Lacy, M.Q.; Hayman, S.R.; Buadi, F.K.; Dingli, D.; Rajkumar, S.V.; Hogan, W.J.; Leung, N.; Grogan, M.; Gertz, M.A. High-dose melphalan and peripheral blood stem cell transplantation for light-chain amyloidosis with cardiac involvement. Blood, 2012, 119(5), 1117-1122. []. [PMID: 22147893].
Levinson, R.T.; Olatoye, O.O.; Randles, E.G.; Howell, K.G.; DiCostanzo, A.C.; Ramirez-Alvarado, M. Role of mutations in the cellular internalization of amyloidogenic light chains into cardiomyocytes. Sci. Rep., 2013, 3, 1278. []. [PMID: 23417147].
Shi, J.; Guan, J.; Jiang, B.; Brenner, D.A.; Del Monte, F.; Ward, J.E.; Connors, L.H.; Sawyer, D.B.; Semigran, M.J.; Macgillivray, T.E.; Seldin, D.C.; Falk, R.; Liao, R. Amyloidogenic light chains induce cardiomyocyte contractile dysfunction and apoptosis via a non-canonical p38alpha MAPK pathway. Proc. Natl. Acad. Sci. USA, 2010, 107(9), 4188-4193. []. [PMID: 20150510].
Sikkink, L.A.; Ramirez-Alvarado, M. Cytotoxicity of amyloidogenic immunoglobulin light chains in cell culture. Cell Death Dis., 2010, 1e98 []. [PMID: 21368874].
Guan, J.; Mishra, S.; Qiu, Y.; Shi, J.; Trudeau, K.; Las, G.; Liesa, M.; Shirihai, O.S.; Connors, L.H.; Seldin, D.C.; Falk, R.H.; MacRae, C.A.; Liao, R. Lysosomal dysfunction and impaired autophagy underlie the pathogenesis of amyloidogenic light chain-mediated cardiotoxicity. EMBO Mol. Med., 2014, 6(11), 1493-1507. []. [PMID: 25319546].
Brenner, D.A.; Jain, M.; Pimentel, D.R.; Wang, B.; Connors, L.H.; Skinner, M.; Apstein, C.S.; Liao, R. Human amyloidogenic light chains directly impair cardiomyocyte function through an increase in cellular oxidant stress. Circ. Res., 2004, 94(8), 1008-1010. []. [PMID: 15044325].
Liao, R.; Jain, M.; Teller, P.; Connors, L.H.; Ngoy, S.; Skinner, M.; Falk, R.H.; Apstein, C.S. Infusion of light chains from patients with cardiac amyloidosis causes diastolic dysfunction in isolated mouse hearts. Circulation, 2001, 104(14), 1594-1597. []. [PMID: 11581134].
Saraiva, M.J. Transthyretin amyloidosis: a tale of weak interactions. FEBS Lett., 2001, 498(2-3), 201-203. []. [PMID: 11412857].
Hammarström, P.; Jiang, X.; Hurshman, A.R.; Powers, E.T.; Kelly, J.W. Sequence-dependent denaturation energetics: A major determinant in amyloid disease diversity. Proc. Natl. Acad. Sci. USA, 2002, 99(Suppl. 4), 16427-16432. []. [PMID: 12351683].
Liao, R.; Ward, J.E. Amyloid cardiomyopathy: Disease on the rise. Circ. Res., 2017, 120(12), 1865-1867. []. [PMID: 28596171].
Bourgault, S.; Choi, S.; Buxbaum, J.N.; Kelly, J.W.; Price, J.L.; Reixach, N. Mechanisms of transthyretin cardiomyocyte toxicity inhibition by resveratrol analogs. Biochem. Biophys. Res. Commun., 2011, 410(4), 707-713. []. [PMID: 21557933].
Victoria, G.S.; Zurzolo, C. The spread of prion-like proteins by lysosomes and tunneling nanotubes: Implications for neurodegenerative diseases. J. Cell Biol., 2017, 216(9), 2633-2644. [PMID: 28724527].
Sanbe, A.; Osinska, H.; Saffitz, J.E.; Glabe, C.G.; Kayed, R.; Maloyan, A.; Robbins, J. Desmin-related cardiomyopathy in transgenic mice: a cardiac amyloidosis. Proc. Natl. Acad. Sci. USA, 2004, 101(27), 10132-10136. []. [PMID: 15220483].
Subramanian, K.; Gianni, D.; Balla, C.; Assenza, G.E.; Joshi, M.; Semigran, M.J.; Macgillivray, T.E.; Van Eyk, J.E.; Agnetti, G.; Paolocci, N.; Bamburg, J.R.; Agrawal, P.B.; Del Monte, F. Cofilin-2 phosphorylation and sequestration in myocardial aggregates: novel pathogenetic mechanisms for idiopathic dilated cardiomyopathy. J. Am. Coll. Cardiol., 2015, 65(12), 1199-1214. []. [PMID: 25814227].
Sidorova, T.N.; Mace, L.C.; Wells, K.S.; Yermalitskaya, L.V.; Su, P.F.; Shyr, Y.; Atkinson, J.B.; Fogo, A.B.; Prinsen, J.K.; Byrne, J.G.; Petracek, M.R.; Greelish, J.P.; Hoff, S.J.; Ball, S.K.; Glabe, C.G.; Brown, N.J.; Barnett, J.V.; Murray, K.T. Hypertension is associated with preamyloid oligomers in human atrium: a missing link in atrial pathophysiology? J. Am. Heart Assoc., 2014, 3(6)e001384 []. [PMID: 25468655].
Despa, S.; Sharma, S.; Harris, T.R.; Dong, H.; Li, N.; Chiamvimonvat, N.; Taegtmeyer, H.; Margulies, K.B.; Hammock, B.D.; Despa, F. Cardioprotection by controlling hyperamylinemia in a “humanized” diabetic rat model. J. Am. Heart Assoc., 2014, 3(4)e001015 []. [PMID: 25146704].
Del Monte, F.; Agnetti, G. Protein post-translational modifications and misfolding: new concepts in heart failure. Proteomics Clin. Appl., 2014, 8(7-8), 534-542. []. [PMID: 24946239].
Sidorova, T.N.; Mace, L.C.; Wells, K.S.; Yermalitskaya, L.V.; Su, P.F.; Shyr, Y.; Byrne, J.G.; Petracek, M.R.; Greelish, J.P.; Hoff, S.J.; Ball, S.K.; Glabe, C.G.; Brown, N.J.; Barnett, J.V.; Murray, K.T. Quantitative imaging of preamyloid oligomers, a novel structural abnormality, in human atrial samples. J. Histochem. Cytochem., 2014, 62(7), 479-487. []. [PMID: 24789805].
Agnetti, G.; Halperin, V.L.; Kirk, J.A.; Chakir, K.; Guo, Y.; Lund, L.; Nicolini, F.; Gherli, T.; Guarnieri, C.; Caldarera, C.M.; Tomaselli, G.F.; Kass, D.A.; Van Eyk, J.E. Desmin modifications associate with amyloid-like oligomers deposition in heart failure. Cardiovasc. Res., 2014, 102(1), 24-34. []. [PMID: 24413773].
Xu, J.; Reumers, J.; Couceiro, J.R.; De Smet, F.; Gallardo, R.; Rudyak, S.; Cornelis, A.; Rozenski, J.; Zwolinska, A.; Marine, J.C.; Lambrechts, D.; Suh, Y.A.; Rousseau, F.; Schymkowitz, J. Gain of function of mutant p53 by coaggregation with multiple tumor suppressors. Nat. Chem. Biol., 2011, 7(5), 285-295. []. [PMID: 21445056].
Gianni, D.; Li, A.; Tesco, G.; McKay, K.M.; Moore, J.; Raygor, K.; Rota, M.; Gwathmey, J.K.; Dec, G.W.; Aretz, T.; Leri, A.; Semigran, M.J.; Anversa, P.; Macgillivray, T.E.; Tanzi, R.E.; del Monte, F. Protein aggregates and novel presenilin gene variants in idiopathic dilated cardiomyopathy. Circulation, 2010, 121(10), 1216-1226. []. [PMID: 20194882].
Agnetti, G.; Bezstarosti, K.; Dekkers, D.H.; Verhoeven, A.J.; Giordano, E.; Guarnieri, C.; Caldarera, C.M.; Van Eyk, J.E.; Lamers, J.M. Proteomic profiling of endothelin-1-stimulated hypertrophic cardiomyocytes reveals the increase of four different desmin species and alpha-B-crystallin. Biochim. Biophys. Acta, 2008, 1784(7-8), 1068-1076. []. [PMID: 18472024].
Marcelli, S.; Corbo, M.; Iannuzzi, F.; Negri, L.; Blandini, F.; Nistico, R.; Feligioni, M. The involvement of post-translational modifications in Alzheimer’s disease. Curr. Alzheimer Res., 2018, 15(4), 313-335. [DOI: 10.2174/1567205014666170505095109]. [PMID: 28474569].
Ren, R.J.; Dammer, E.B.; Wang, G.; Seyfried, N.T.; Levey, A.I. Proteomics of protein post-translational modifications implicated in neurodegeneration. Transl. Neurodegener., 2014, 3(1), 23. []. [PMID: 25671099].
Schmid, A.W.; Fauvet, B.; Moniatte, M.; Lashuel, H.A. Alpha-synuclein post-translational modifications as potential biomarkers for Parkinson disease and other synucleinopathies. Mol. Cell. Proteomics, 2013, 12(12), 3543-3558. []. [PMID: 23966418].
Agnetti, G.; Husberg, C.; Van Eyk, J.E. Divide and conquer: the application of organelle proteomics to heart failure. Circ. Res., 2011, 108(4), 512-526. []. [PMID: 21335433].
Comenzo, R.L.; Gertz, M.A. Autologous stem cell transplantation for primary systemic amyloidosis. Blood, 2002, 99(12), 4276-4282. []. [PMID: 12036853].
Dispenzieri, A.; Buadi, F.; Kumar, S.K.; Reeder, C.B.; Sher, T.; Lacy, M.Q.; Kyle, R.A.; Mikhael, J.R.; Roy, V.; Leung, N.; Grogan, M.; Kapoor, P.; Lust, J.A.; Dingli, D.; Go, R.S.; Hwa, Y.L.; Hayman, S.R.; Fonseca, R.; Ailawadhi, S.; Bergsagel, P.L.; Chanan-Khan, A.; Rajkumar, S.V.; Russell, S.J.; Stewart, K.; Zeldenrust, S.R.; Gertz, M.A. Treatment of immunoglobulin light chain amyloidosis: mayo stratification of myeloma and risk-adapted therapy (mSMART) consensus statement. Mayo Clin. Proc., 2015, 90(8), 1054-1081. []. [PMID: 26250727].
Palladini, G.; Perfetti, V.; Obici, L.; Caccialanza, R.; Semino, A.; Adami, F.; Cavallero, G.; Rustichelli, R.; Virga, G.; Merlini, G. Association of melphalan and high-dose dexamethasone is effective and well tolerated in patients with AL (primary) amyloidosis who are ineligible for stem cell transplantation. Blood, 2004, 103(8), 2936-2938. []. [PMID: 15070667].
Kyle, R.A.; Gertz, M.A.; Greipp, P.R.; Witzig, T.E.; Lust, J.A.; Lacy, M.Q.; Therneau, T.M. A trial of three regimens for primary amyloidosis: colchicine alone, melphalan and prednisone, and melphalan, prednisone, and colchicine. N. Engl. J. Med., 1997, 336(17), 1202-1207. []. [PMID: 9110907].
Maurer, M.S.; Elliott, P.; Comenzo, R.; Semigran, M.; Rapezzi, C. Addressing common questions encountered in the diagnosis and management of cardiac amyloidosis. Circulation, 2017, 135(14), 1357-1377. []. [PMID: 28373528].
Reece, D.E.; Hegenbart, U.; Sanchorawala, V.; Merlini, G.; Palladini, G.; Bladé, J.; Fermand, J.P.; Hassoun, H.; Heffner, L.; Kukreti, V.; Vescio, R.A.; Pei, L.; Enny, C.; Esseltine, D.L.; van de Velde, H.; Cakana, A.; Comenzo, R.L. Long-term follow-up from a phase 1/2 study of single-agent bortezomib in relapsed systemic AL amyloidosis. Blood, 2014, 124(16), 2498-2506. []. [PMID: 25202139].
Dubrey, S.W.; Reece, D.E.; Sanchorawala, V.; Hegenbart, U.; Merlini, G.; Palladini, G.; Fermand, J.P.; Vescio, R.A.; Bladé, J.; Heffner, L.T.; Hassoun, H.; Liu, X.; Enny, C.; Ramaswami, P.; Elsayed, Y.; Van De Velde, H.; Mortimer, S.; Cakana, A.; Comenzo, R.L. Bortezomib in a phase 1 trial for patients with relapsed AL amyloidosis: cardiac responses and overall effects. QJM, 2011, 104(11), 957-970. []. [PMID: 21752867].
Kastritis, E.; Leleu, X.; Arnulf, B.; Zamagni, E.; Cibeira, M.T.; Kwok, F.; Mollee, P.; Hájek, R.; Moreau, P.; Jaccard, A.; Schönland, S.; Filshie, R.; Nicolas-Virelizier, E.; Augustson, B.; Mateos, M.V.; Wechalekar, A.; Hachulla, E.; Milani, P.; Dimopoulos, M.A.; Fermand, J.P.; Foli, A.; Gavriatopoulou, M.; Palumbo, A.; Sonneveld, P.; Johnsen, H.E.; Merlini, G.; Palladini, G. A randomized phase III trial of melphalan and dexamethasone (MDex) versus bortezomib, melphalan and dexamethasone (BMDex) for untreated patients with AL amyloidosis. Clin. Lymphoma Myeloma Leuk., 2015, 15, e59-e60. [].
Alahwal, H.; Song, K.W.; Duggan, P.; Sutherland, H.J.; Neri, P.; Broady, R.; Bahlis, N.J.; Jimenez-Zepeda, V. Bortezomib-containing regimens for the treatment of newly diagnosed al amyloidosis: Experience of two centers in Canada. Blood, 2016, 128(22), 2131-2131.
Sidana, S.; Tandon, N.; Dispenzieri, A.; Gertz, M.A.; Buadi, F.; Lacy, M.Q.; Dingli, D.; Fonder, A.; Hayman, S.R.; Hobbs, M.; Gonsalves, W.I.; Hwa, Y.L.; Kapoor, P.; Kyle, R.A.; Leung, N.; Go, R.S.; Lust, J.A.; Russell, S.J.; Zeldenrust, S.R.; Rajkumar, S.V.; Kumar, S. Bortezomib versus non-bortezomib based treatment for transplant ineligible patients with light chain amyloidosis. Blood, 2016, 128(22), 3317-3317.
Milani, P.; Gertz, M.A.; Merlini, G.; Dispenzieri, A. Attitudes about when and how to treat patients with AL amyloidosis: an international survey. Amyloid, 2017, 24(4), 213-216. []. [PMID: 28857614].
Venner, C.P.; Lane, T.; Foard, D.; Rannigan, L.; Gibbs, S.D.; Pinney, J.H.; Whelan, C.J.; Lachmann, H.J.; Gillmore, J.D.; Hawkins, P.N.; Wechalekar, A.D. Cyclophosphamide, bortezomib, and dexamethasone therapy in AL amyloidosis is associated with high clonal response rates and prolonged progression-free survival. Blood, 2012, 119(19), 4387-4390. []. [PMID: 22331187].
Mikhael, J.R.; Schuster, S.R.; Jimenez-Zepeda, V.H.; Bello, N.; Spong, J.; Reeder, C.B.; Stewart, A.K.; Bergsagel, P.L.; Fonseca, R. Cyclophosphamide-bortezomib-dexamethasone (CyBorD) produces rapid and complete hematologic response in patients with AL amyloidosis. Blood, 2012, 119(19), 4391-4394. []. [PMID: 22331188].
Jaccard, A.; Comenzo, R.L.; Hari, P.; Hawkins, P.N.; Roussel, M.; Morel, P.; Macro, M.; Pellegrin, J.L.; Lazaro, E.; Mohty, D.; Mercie, P.; Decaux, O.; Gillmore, J.; Lavergne, D.; Bridoux, F.; Wechalekar, A.D.; Venner, C.P. Efficacy of bortezomib, cyclophosphamide and dexamethasone in treatment-naïve patients with high-risk cardiac AL amyloidosis (Mayo Clinic stage III). Haematologica, 2014, 99(9), 1479-1485. []. [PMID: 24859879].
Sanchorawala, V.; Palladini, G.; Kukreti, V.; Zonder, J.A.; Cohen, A.D.; Seldin, D.C.; Dispenzieri, A.; Jaccard, A.; Schönland, S.O.; Berg, D.; Yang, H.; Gupta, N.; Hui, A.M.; Comenzo, R.L.; Merlini, G. A phase 1/2 study of the oral proteasome inhibitor ixazomib in relapsed or refractory AL amyloidosis. Blood, 2017, 130(5), 597-605. []. [PMID: 28550039].
McBride, A.; Klaus, J.O.; Stockerl-Goldstein, K. Carfilzomib: a second-generation proteasome inhibitor for the treatment of multiple myeloma. Am. J. Health Syst. Pharm., 2015, 72(5), 353-360. []. [PMID: 25694410].
Dimopoulos, M.A.; Goldschmidt, H.; Niesvizky, R.; Joshua, D.; Chng, W.J.; Oriol, A.; Orlowski, R.Z.; Ludwig, H.; Facon, T.; Hajek, R.; Weisel, K.; Hungria, V.; Minuk, L.; Feng, S.; Zahlten-Kumeli, A.; Kimball, A.S.; Moreau, P. Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial. Lancet Oncol., 2017, 18(10), 1327-1337. []. [PMID: 28843768].
Lokhorst, H.M.; Plesner, T.; Laubach, J.P.; Nahi, H.; Gimsing, P.; Hansson, M.; Minnema, M.C.; Lassen, U.; Krejcik, J.; Palumbo, A.; van de Donk, N.W.; Ahmadi, T.; Khan, I.; Uhlar, C.M.; Wang, J.; Sasser, A.K.; Losic, N.; Lisby, S.; Basse, L.; Brun, N.; Richardson, P.G. Targeting CD38 with daratumumab monotherapy in multiple myeloma. N. Engl. J. Med., 2015, 373(13), 1207-1219. []. [PMID: 26308596].
Kaufman, G.P.; Schrier, S.L.; Lafayette, R.A.; Arai, S.; Witteles, R.M.; Liedtke, M. Daratumumab yields rapid and deep hematologic responses in patients with heavily pretreated AL amyloidosis. Blood, 2017, 130(7), 900-902. []. [PMID: 28615223].
Pepys, M.B.; Herbert, J.; Hutchinson, W.L.; Tennent, G.A.; Lachmann, H.J.; Gallimore, J.R.; Lovat, L.B.; Bartfai, T.; Alanine, A.; Hertel, C.; Hoffmann, T.; Jakob-Roetne, R.; Norcross, R.D.; Kemp, J.A.; Yamamura, K.; Suzuki, M.; Taylor, G.W.; Murray, S.; Thompson, D.; Purvis, A.; Kolstoe, S.; Wood, S.P.; Hawkins, P.N. Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis. Nature, 2002, 417(6886), 254-259. []. [PMID: 12015594].
Bodin, K.; Ellmerich, S.; Kahan, M.C.; Tennent, G.A.; Loesch, A.; Gilbertson, J.A.; Hutchinson, W.L.; Mangione, P.P.; Gallimore, J.R.; Millar, D.J.; Minogue, S.; Dhillon, A.P.; Taylor, G.W.; Bradwell, A.R.; Petrie, A.; Gillmore, J.D.; Bellotti, V.; Botto, M.; Hawkins, P.N.; Pepys, M.B. Antibodies to human serum amyloid P component eliminate visceral amyloid deposits. Nature, 2010, 468(7320), 93-97. []. [PMID: 20962779].
Richards, D.B.; Cookson, L.M.; Berges, A.C.; Barton, S.V.; Lane, T.; Ritter, J.M.; Fontana, M.; Moon, J.C.; Pinzani, M.; Gillmore, J.D.; Hawkins, P.N.; Pepys, M.B. Therapeutic clearance of amyloid by antibodies to serum amyloid P component. N. Engl. J. Med., 2015, 373(12), 1106-1114. []. [PMID: 26176329].
Gertz, M.A.; Landau, H.; Comenzo, R.L.; Seldin, D.; Weiss, B.; Zonder, J.; Merlini, G.; Schönland, S.; Walling, J.; Kinney, G.G.; Koller, M.; Schenk, D.B.; Guthrie, S.D.; Liedtke, M. First-in-human phase I/II study of NEOD001 in patients with light chain amyloidosis and persistent organ dysfunction. J. Clin. Oncol., 2016, 34(10), 1097-1103. []. [PMID: 26858336].
Gertz, M.A.; Comenzo, R.L.; Landau, H.; Sanchorawala, V.; Weiss, B.M.; Zonder, J.A.; Walling, J.; Kinney, G.G.; Koller, M.; Schenk, D.B.; Guthrie, S.D.; Liu, E.; Liedtke, M. NEOD001 demonstrates organ biomarker responses in patients with light chain amyloidosis and persistent organ dysfunction: Results from the expansion cohort of a phase 1/2 study. Blood, 2016, 128(22), 644-644.
Langer, A.L.; Miao, S.; Mapara, M.; Radhakrishnan, J.; Maurer, M.; Raza, S.; Mears, J.; Solomon, A.; Lentzsch, S. 188 results of phase I study of chimeric fibril-reactive monoclonal antibody 11-1F4 in patients with AL amyloi-dosis. Blood, 2015, 126, 188.
Edwards, C.V.; Gould, J.; Langer, A.L.; Mapara, M.; Radhakrishnan, J.; Maurer, M.S.; Raza, S.; Mears, J.G.; Wall, J.S.; Solomon, A.; Lentzsch, S. Analysis of the Phase 1a/b Study of Chimeric Fibril-Reactive Monoclonal Antibody 11-1F4 in Patients with AL Amyloidosis. Blood, 2016, 128(22), 643-643.
Wechalekar, A.D.; Whelan, C. Encouraging impact of doxycycline on early mortality in cardiac light chain (AL) amyloidosis. Blood Cancer J., 2017, 7(3)e546 []. [PMID: 28338670].
Wechalekar, A.D.; Whelan, C. Encouraging impact of doxycycline on early mortality in cardiac light chain (AL) amyloidosis. Blood Cancer J., 2017, 7(3)e546 []. [PMID: 28338670].
Ericzon, B.G.; Wilczek, H.E.; Larsson, M.; Wijayatunga, P.; Stangou, A.; Pena, J.R.; Furtado, E.; Barroso, E.; Daniel, J.; Samuel, D.; Adam, R.; Karam, V.; Poterucha, J.; Lewis, D.; Ferraz-Neto, B.H.; Cruz, M.W.; Munar-Ques, M.; Fabregat, J.; Ikeda, S.; Ando, Y.; Heaton, N.; Otto, G.; Suhr, O. Liver Transplantation for Hereditary Transthyretin Amyloidosis: After 20 Years Still the Best Therapeutic Alternative? Transplantation, 2015, 99(9), 1847-1854. []. [PMID: 26308415].
Suhr, O.B.; Larsson, M.; Ericzon, B-G.; Wilczek, H.E. Survival After Transplantation in Patients With Mutations Other Than Val30Met: Extracts From the FAP World Transplant Registry. Transplantation, 2016, 100(2), 373-381. []. [PMID: 26656838].
Coelho, T.; Adams, D.; Silva, A.; Lozeron, P.; Hawkins, P.N.; Mant, T.; Perez, J.; Chiesa, J.; Warrington, S.; Tranter, E.; Munisamy, M.; Falzone, R.; Harrop, J.; Cehelsky, J.; Bettencourt, B.R.; Geissler, M.; Butler, J.S.; Sehgal, A.; Meyers, R.E.; Chen, Q.; Borland, T.; Hutabarat, R.M.; Clausen, V.A.; Alvarez, R.; Fitzgerald, K.; Gamba-Vitalo, C.; Nochur, S.V.; Vaishnaw, A.K.; Sah, D.W.; Gollob, J.A.; Suhr, O.B. Safety and efficacy of RNAi therapy for transthyretin amyloidosis. N. Engl. J. Med., 2013, 369(9), 819-829. []. [PMID: 23984729].
van Rooij, E.; Olson, E.N. MicroRNA therapeutics for cardiovascular disease: opportunities and obstacles. Nat. Rev. Drug Discov., 2012, 11(11), 860-872. []. [PMID: 23080337].
Benson, M.D.; Dasgupta, N.R.; Rissing, S.M.; Smith, J.; Feigenbaum, H. Safety and efficacy of a TTR specific antisense oligonucleotide in patients with transthyretin amyloid cardiomyopathy. Amyloid, 2017, 24(4), 219-225. []. [PMID: 28906150].
Adams, D.; Suhr, O.B.; Dyck, P.J.; Litchy, W.J.; Leahy, R.G.; Chen, J.; Gollob, J.; Coelho, T. Trial design and rationale for APOLLO, a Phase 3, placebo-controlled study of patisiran in patients with hereditary ATTR amyloidosis with polyneuropathy. BMC Neurol., 2017, 17(1), 181. []. [PMID: 28893208].
Adams, D.; Coelho, T.; Conceicao, I.; Cruz, M.W.; Schmidt, H.; Buades, J.; Campistol, J.; Pouget, J.; Berk, J.; Polydefkis, M.; Ziyadeh, N.; Partisano, A.; Chen, J.; Sweetser, M.; Gollob, J.; Suhr, O. Phase 2 Open-Label Extension (OLE) Study of Patisiran, an Investigational RNAi Therapeutic for the Treatment of Polyneuropathy due to Hereditary ATTR (hATTR) Amyloidosis: 24-month safety and efficacy in subgroup of patients with cardiac involvement. ESC Heart Failure Congress, Paris, FR2017, Vol. 19, pp. 5-601.
Berk, J.L.; Suhr, O.B.; Obici, L.; Sekijima, Y.; Zeldenrust, S.R.; Yamashita, T.; Heneghan, M.A.; Gorevic, P.D.; Litchy, W.J.; Wiesman, J.F.; Nordh, E.; Corato, M.; Lozza, A.; Cortese, A.; Robinson-Papp, J.; Colton, T.; Rybin, D.V.; Bisbee, A.B.; Ando, Y.; Ikeda, S.; Seldin, D.C.; Merlini, G.; Skinner, M.; Kelly, J.W.; Dyck, P.J. Repurposing diflunisal for familial amyloid polyneuropathy: a randomized clinical trial. JAMA, 2013, 310(24), 2658-2667. []. [PMID: 24368466].
Castaño, A.; Helmke, S.; Alvarez, J.; Delisle, S.; Maurer, M.S. Diflunisal for ATTR cardiac amyloidosis. Congest. Heart Fail., 2012, 18(6), 315-319. []. [PMID: 22747647].
Ponikowski, P.; Voors, A.A.; Anker, S.D.; Bueno, H.; Cleland, J.G.; Coats, A.J.; Falk, V.; González-Juanatey, J.R.; Harjola, V.P.; Jankowska, E.A.; Jessup, M.; Linde, C.; Nihoyannopoulos, P.; Parissis, J.T.; Pieske, B.; Riley, J.P.; Rosano, G.M.; Ruilope, L.M.; Ruschitzka, F.; Rutten, F.H.; van der Meer, P. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur. Heart J., 2016, 37(27), 2129-2200. []. [PMID: 27206819].
Bulawa, C.E.; Connelly, S.; Devit, M.; Wang, L.; Weigel, C.; Fleming, J.A.; Packman, J.; Powers, E.T.; Wiseman, R.L.; Foss, T.R.; Wilson, I.A.; Kelly, J.W.; Labaudinière, R. Tafamidis, a potent and selective transthyretin kinetic stabilizer that inhibits the amyloid cascade. Proc. Natl. Acad. Sci. USA, 2012, 109(24), 9629-9634. []. [PMID: 22645360].
Maurer, M.S.; Grogan, D.R.; Judge, D.P.; Mundayat, R.; Packman, J.; Lombardo, I.; Quyyumi, A.A.; Aarts, J.; Falk, R.H. Tafamidis in transthyretin amyloid cardiomyopathy: effects on transthyretin stabilization and clinical outcomes. Circ Heart Fail, 2015, 8(3), 519-526. []. [PMID: 25872787].
Damy, T.; Judge, D.P.; Kristen, A.V.; Berthet, K.; Li, H.; Aarts, J. Cardiac findings and events observed in an open-label clinical trial of tafamidis in patients with non-Val30Met and non-Val122Ile hereditary transthyretin amyloidosis. J. Cardiovasc. Transl. Res., 2015, 8(2), 117-127. []. [PMID: 25743445].
Maurer, M.S.; Elliott, P.; Merlini, G.; Shah, S.J.; Cruz, M.W.; Flynn, A.; Gundapaneni, B.; Hahn, C.; Riley, S.; Schwartz, J.; Sultan, M.B.; Rapezzi, C. Design and Rationale of the Phase 3 ATTR-ACT Clinical Trial (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial). Circ Heart Fail, 2017, 10(6)e003815 []. [PMID: 28611125].
Kristen, A.V.; Lehrke, S.; Buss, S.; Mereles, D.; Steen, H.; Ehlermann, P.; Hardt, S.; Giannitsis, E.; Schreiner, R.; Haberkorn, U.; Schnabel, P.A.; Linke, R.P.; Röcken, C.; Wanker, E.E.; Dengler, T.J.; Altland, K.; Katus, H.A. Green tea halts progression of cardiac transthyretin amyloidosis: an observational report. Clin. Res. Cardiol., 2012, 101(10), 805-813. []. [PMID: 22584381].
Ferreira, N.; Saraiva, M.J.; Almeida, M.R. Natural polyphenols inhibit different steps of the process of transthyretin (TTR) amyloid fibril formation. FEBS Lett., 2011, 585(15), 2424-2430. []. [PMID: 21740906].
Cardoso, I.; Martins, D.; Ribeiro, T.; Merlini, G.; Saraiva, M.J. Synergy of combined doxycycline/TUDCA treatment in lowering Transthyretin deposition and associated biomarkers: studies in FAP mouse models. J. Transl. Med., 2010, 8, 74. []. [PMID: 20673327].
Cardoso, I.; Saraiva, M.J. Doxycycline disrupts transthyretin amyloid: evidence from studies in a FAP transgenic mice model. FASEB J., 2006, 20(2), 234-239. []. [PMID: 16449795].
Macedo, B.; Batista, A.R.; Ferreira, N.; Almeida, M.R.; Saraiva, M.J. Anti-apoptotic treatment reduces transthyretin deposition in a transgenic mouse model of Familial Amyloidotic Polyneuropathy. Biochim. Biophys. Acta, 2008, 1782(9), 517-522. []. [PMID: 18572024].
Obici, L.; Cortese, A.; Lozza, A.; Lucchetti, J.; Gobbi, M.; Palladini, G.; Perlini, S.; Saraiva, M.J.; Merlini, G. Doxycycline plus tauroursodeoxycholic acid for transthyretin amyloidosis: a phase II study. Amyloid, 2012, 19(Suppl. 1), 34-36. []. [PMID: 22551192].
Higaki, J.N.; Chakrabartty, A.; Galant, N.J.; Hadley, K.C.; Hammerson, B.; Nijjar, T.; Torres, R.; Tapia, J.R.; Salmans, J.; Barbour, R.; Tam, S.J.; Flanagan, K.; Zago, W.; Kinney, G.G. Novel conformation-specific monoclonal antibodies against amyloidogenic forms of transthyretin. Amyloid, 2016, 23(2), 86-97. []. [PMID: 26981744].
Maloyan, A.; Gulick, J.; Glabe, C.G.; Kayed, R.; Robbins, J. Exercise reverses preamyloid oligomer and prolongs survival in alphaB-crystallin-based desmin-related cardiomyopathy. Proc. Natl. Acad. Sci. USA, 2007, 104(14), 5995-6000. []. [PMID: 17389375].
Vila-Rico, M.; Colome-Calls, N.; Martin-Castel, L.; Gay, M.; Azorin, S.; Vilaseca, M.; Planas, A.; Canals, F. Quantitative analysis of post-translational modifications in human serum transthyretin associated with familial amyloidotic polyneuropathy by targeted LC-MS and intact protein MS. J Proteomics, , 2015, 127(Pt B). , 234- 246.
Nakanishi, T.; Yoshioka, M.; Moriuchi, K.; Yamamoto, D.; Tsuji, M.; Takubo, T. S-sulfonation of transthyretin is an important trigger step in the formation of transthyretin-related amyloid fibril. Biochim. Biophys. Acta, 2010, 1804(7), 1449-1456. []. [PMID: 20388560].
Jensen, B.C.; Willis, M.S. The Head and the Heart: The Alzheimer’s Connection. J. Am. Coll. Cardiol., 2016, 68(22), 2408-2411. []. [PMID: 27908344].
Bravo, P.E.; Dorbala, S. Targeted Nuclear Imaging Probes for Cardiac Amyloidosis. Curr. Cardiol. Rep., 2017, 19(7), 59. []. [PMID: 28508350].

Rights & Permissions Print Export Cite as
© 2023 Bentham Science Publishers | Privacy Policy