Effect of doxycycline and ursodeoxycholic acid on transthyretin amyloidosis

Wixner, Jonas; Pilebro, Björn; Lundgren, Hans-Erik; Olsson, Malin; Anan, Intissar

doi:10.1080/13506129.2016.1269739

Cited by 37 publications

(25 citation statements)

References 4 publications

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“…58 The preliminary data showed that Doxy/TUDCA stabilizes the disease for 1 year with an acceptable toxicity profile. 58 Doxy/…”

Section: Drugs Affecting Degradation and Reabsorption Of Amyloid Fimentioning

confidence: 96%

“…TUDCA is now being tested in a phase 3 clinical trial (NCT03481972). 58,59 Miridesap Miridesap is an antibody that targets serum amyloid P protein (SAP) or amyloid fibrils. SAP, a normal plasma glycoprotein synthesized by the liver, stabilizes and protects amyloid fibrils from proteolytic degradation.…”

Section: Drugs Affecting Degradation and Reabsorption Of Amyloid Fimentioning

confidence: 99%

“…Doxy/TUDCA appears to be effective in vitro in causing complete disaggregation of amyloid fibers and generating nontoxic molecular species 58 . In a small phase 2 open label study, treatment with Doxy/TUDCA was well tolerated and resulted in no progression of cardiac involvement and neuropathy 58 . The preliminary data showed that Doxy/TUDCA stabilizes the disease for 1 year with an acceptable toxicity profile 58 .…”

Section: Treatmentmentioning

confidence: 99%

“…In a small phase 2 open label study, treatment with Doxy/TUDCA was well tolerated and resulted in no progression of cardiac involvement and neuropathy 58 . The preliminary data showed that Doxy/TUDCA stabilizes the disease for 1 year with an acceptable toxicity profile 58 . Doxy/TUDCA is now being tested in a phase 3 clinical trial (NCT03481972) 58,59 …”

Section: Treatmentmentioning

confidence: 99%

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Diagnosis and treatment of transthyretin‐related amyloidosis cardiomyopathy

Teng

Bae

et al. 2020

Clinical Cardiology

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Transthyretin-related amyloidosis (ATTR) is a subgroup of amyloidosis that results from extracellular misassembled and toxic amyloid deposits affecting multiple organ systems, and cardiac tissues in particular. Because ATTR often presents as heart failure with preserved ejection fraction (HFpEF), it has been largely underdiagnosed. Once considered incurable with a grave prognosis, ATTR cardiomyopathy has seen the development of promising alternatives for diagnosis and treatment, with early diagnosis and treatment of ATTR cardiomyopathy highly beneficial due to its high mortality rate. For instance, diagnosing ATTR cardiomyopathy previously required a cardiac biopsy, but new modalities, such as cardiac magnetic resonance imaging and radionuclide bone scans, show promise in accurately diagnosing ATTR cardiomyopathy. Ongoing research and clinical trials have focused on identifying new treatments which primarily target amyloid fiber formation by inhibiting TTR gene expression, stabilizing the TTR tetramer, preventing oligomer aggregation, or affecting degradation of amyloid fibers. In this review, we describe the advances made in the diagnosis and treatment of ATTR in order to increase awareness of the disease and encourage a lower threshold for ATTR workup. Our review also highlights the need for improving the screening, diagnosis, and treatment guidelines for ATTR cardiomyopathy. K E Y W O R D S heart disease, physical diagnosis/cardiovascular, treatment 1 | BACKGROUND Transthyretin (TTR)-related amyloidosis (ATTR), a rare and underdiagnosed disease, mainly affects the cardiac and peripheral nerves and is fatal if not treated in time. 1 Primarily synthesized in the liver, TTR is a protein that transports vitamin A and thyroxine in plasma and cerebrospinal fluid. 2 The mechanism of transportation involves four oligomers that attach to each other to form two dimers, which in turn form a TTR tetramer that contains the hormone binding site. 2 Through gene mutation or aging of the protein, TTR can become unstable and break up into oligomers, which aggregate into insoluble fibrils called TTR amyloid that deposit into extracellular space or tissues, causing ATTR. 3 Based on the type of precursor and misfolded protein amyloids, there are different types of amyloid diseases from ATTR to light chain amyloidosis (AL), which is caused by aggregation of immunoglobulin light chains produced by plasma cells in the bone marrow. 4 Depending on the type of precursor protein, different protein amyloids target Catherine Teng and Pengyang Li contributed equally to this review article.

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“…58 The preliminary data showed that Doxy/TUDCA stabilizes the disease for 1 year with an acceptable toxicity profile. 58 Doxy/…”

Section: Drugs Affecting Degradation and Reabsorption Of Amyloid Fimentioning

confidence: 96%

Section: Drugs Affecting Degradation and Reabsorption Of Amyloid Fimentioning

confidence: 99%

Section: Treatmentmentioning

confidence: 99%

Section: Treatmentmentioning

confidence: 99%

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Diagnosis and treatment of transthyretin‐related amyloidosis cardiomyopathy

Teng

Bae

et al. 2020

Clinical Cardiology

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“…W czasie leczenia nie obserwowano progresji zarówno HF, jak i polineuropatii, co sugeruje, że terapia skojarzona wykazuje stabilizujący wpływ na przebieg kliniczny ATTR. Wobec zachęcających wyników zainicjowano kolejne badanie II fazy, w którym zostaną ocenione aktywność kliniczna i profil bezpieczeństwa doksycykliny w skojarzeniu z kwasem ursodeoksycholowym w leczeniu pacjentów z ATTR [38].…”

Section: Aktywność Doksycykliny W Leczeniu Pacjentów Z Attrunclassified

Doksycyklina w terapii amyloidozy układowej z zajęciem serca

Łyczkowska-Piotrowska

Salomon-Perzyński

Końska

et al. 2018

Hematologia

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W leczeniu chorych na amyloidozy układowe dominują obecnie strategie ukierunkowane na zmniejszenie produkcji białek prekursorowych amyloidu. Takie podejście jest między innymi reprezentowane przez stosowanie chemioterapii w amyloidozie łańcuchów lekkich (amyloidozie AL) lub transplantację wątroby czy próby supresji ekspresji genu transtyretyny u chorych na amyloidozy transtyretynowe (ATTR). Ostatnio jednak coraz aktywniej są rozwijane terapie służące ograniczeniu powstawania amyloidu z krążących prekursorów lub eliminacji już uformowanych depozytów amyloidowych. Do tej grupy metod można zaliczyć przewlekłe stosowanie doksycykliny, powszechnie znanego antybiotyku bakteriostatycznego z grupy tetracyklin. W badaniach przedklinicznych wykazano, że potencjał antyamyloidogenny doksycykliny w amyloidozie AL polega zarówno na interferencji w proces amyloidogenezy, jak i destrukcji depozytów amyloidowych. Kliniczne badania retrospektywne wskazują, że doksycyklina stosowana wraz ze standardową chemioterapią poprawia rokowanie u chorych na amyloidozę AL z zajęciem serca, którzy stanowią najgorzej rokującą grupę pacjentów, zachowując przy tym korzystny profil bezpieczeństwa terapii. Z kolei wydaje się, że w ATTR doksycyklina stablizuje przebieg kliniczny choroby. W pracy dokonano przeglądu piśmiennictwa dotyczącego roli doksycykliny w leczeniu chorych na amyloidozy układowe.

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Progress and challenges in the treatment of cardiac amyloidosis: a review of the literature

et al. 2021

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Cardiac amyloidosis is a restrictive cardiomyopathy determined by the accumulation of amyloid, which is represented by misfolded protein fragments in the cardiac extracellular space. The main classification of systemic amyloidosis is determined by the amyloid precursor proteins causing a very heterogeneous disease spectrum, but the main types of amyloidosis involving the heart are light chain (AL) and transthyretin amyloidosis (ATTR). AL, in which the amyloid precursor is represented by misfolded immunoglobulin light chains, can involve almost any system carrying the worst prognosis among amyloidosis patients. This has however dramatically improved in the last few years with the increased usage of the novel therapies such as proteasome inhibitors and haematopoietic cell transplantation, in the case of timely diagnosis and initiation of treatment. The treatment for AL is directed by the haematologist working closely with the cardiologist when there is a significant cardiac involvement. Transthyretin (TTR) is a protein that is produced by the liver and is involved in the transportation of thyroid hormones, especially thyroxine and retinol binding protein. ATTR results from the accumulation of transthyretin amyloid in the extracellular space of different organs and systems, especially the heart and the nervous system. Specific therapies for ATTR act at various levels of TTR, from synthesis to deposition: TTR tetramer stabilization, oligomer aggregation inhibition, genetic therapy, amyloid fibre degradation, antiserum amyloid P antibodies, and antiserum TTR antibodies. Treatment of systemic amyloidosis has dramatically evolved over the last few years in both AL and ATTR, improving disease prognosis. Moreover, recent studies revealed that timely treatment can lead to an improvement in clinical status and in a regression of amyloid myocardial infiltration showed by imaging, especially by cardiac magnetic resonance, in both AL and ATTR. However, treating cardiac amyloidosis is a complex task due to the frequent association between systemic congestion and low blood pressure, thrombo-embolic and haemorrhagic risk balance, patient frailty, and generally poor prognosis. The aim of this review is to describe the current state of knowledge regarding cardiac amyloidosis therapy in this constantly evolving field, classified as treatment of the cardiac complications of amyloidosis (heart failure, rhythm and conduction disturbances, and thrombo-embolic risk) and the disease-modifying therapy.

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Effect of doxycycline and ursodeoxycholic acid on transthyretin amyloidosis

Cited by 37 publications

References 4 publications

Diagnosis and treatment of transthyretin‐related amyloidosis cardiomyopathy

Diagnosis and treatment of transthyretin‐related amyloidosis cardiomyopathy

Doksycyklina w terapii amyloidozy układowej z zajęciem serca

Progress and challenges in the treatment of cardiac amyloidosis: a review of the literature

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