Academic literature on the topic 'ATTR amyloidosys'
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Journal articles on the topic "ATTR amyloidosys"
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Ablasser, Klemens, Nicolas Verheyen, Theresa Glantschnig, Giulio Agnetti, and Peter P. Rainer. "Unfolding Cardiac Amyloidosis –From Pathophysiology to Cure." Current Medicinal Chemistry 26, no. 16 (August 26, 2019): 2865–78. http://dx.doi.org/10.2174/0929867325666180104153338.
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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.
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Musetti, Veronica, Francesco Greco, Vincenzo Castiglione, Alberto Aimo, Cataldo Palmieri, Dario Genovesi, Assuero Giorgetti, et al. "Tissue Characterization in Cardiac Amyloidosis." Biomedicines 10, no. 12 (November 28, 2022): 3054. http://dx.doi.org/10.3390/biomedicines10123054.
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Cardiac amyloidosis (CA) has long been considered a rare disease, but recent advancements in diagnostic tools have led to a reconsideration of the epidemiology of CA. Amyloid light-chain (AL) and transthyretin (ATTR) amyloidoses are the most common forms of cardiac amyloidosis. Due to the distinct treatments and the different prognoses, amyloid typing is crucial. Although a non-biopsy diagnosis can be obtained in ATTR amyloidosis when certain diagnostic criteria are fulfilled, tissue characterization still represents the gold standard for the diagnosis and typing of CA, particularly in AL amyloidosis. The present review focuses on the status of tissue characterization in cardiac amyloidosis, from histochemistry to immunohistochemistry and mass spectrometry, as well as on its future directions.
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Hund, Ernst, Arnt Kristen, Michaela Auer-Grumbach, Christian Geber, Frank Birklein, Wilhelm Schulte-Mattler, Claudia Sommer, Hartmut Schmidt, and Christoph Röcken. "Transthyretin-Amyloidose (ATTR-Amyloidose): Empfehlungen zum Management in Deutschland und Österreich." Aktuelle Neurologie 45, no. 08 (September 14, 2018): 605–16. http://dx.doi.org/10.1055/a-0649-0724.
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ZusammenfassungDie Transthyretin-Amyloidose (ATTR-Amyloidose) ist eine seltene, rasch verlaufende neurodegenerative Erkrankung, verursacht durch Mutationen im Transthyretin-Gen. Aufgrund der Seltenheit ist sie wenig bekannt mit der Folge, dass die Diagnose in vielen Fällen nicht oder für eine effektive Therapie zu spät gestellt wird. Therapeutisch steht seit Anfang der 1990er-Jahre die Lebertransplantation zur Verfügung, seit 2011 der oral einzunehmende Transthyretinstabilisator Tafamidis. Weitere Substanzen sind in der klinischen Prüfung oder stehen vor der Zulassung. Hierzu zählen die gentherapeutischen Substanzen Inotersen und Patisiran, die auf dem Boden der RNA-Interferenz wirken, für die Behandlung der Polyneuropathie und Tafamidis zur Behandlung der Kardiomyopathie bei ATTR-Amyloidosen. Die vorliegende Arbeit deutschsprachiger Experten gibt Empfehlungen zu Diagnostik, Management und Therapie von ATTR-Amyloidosen und soll helfen, diese erbliche, heute aber gut behandelbare, Erkrankung einem weiteren Kreis von Ärzten bekannt zu machen.
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Park, Gil Yong, Angelo Jamerlan, Kyu Hwan Shim, and Seong Soo A. An. "Diagnostic and Treatment Approaches Involving Transthyretin in Amyloidogenic Diseases." International Journal of Molecular Sciences 20, no. 12 (June 18, 2019): 2982. http://dx.doi.org/10.3390/ijms20122982.
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Transthyretin (TTR) is a thyroid hormone-binding protein which transports thyroxine from the bloodstream to the brain. The structural stability of TTR in tetrameric form is crucial for maintaining its original functions in blood or cerebrospinal fluid (CSF). The altered structure of TTR due to genetic mutations or its deposits due to aggregation could cause several deadly diseases such as cardiomyopathy and neuropathy in autonomic, motor, and sensory systems. The early diagnoses for hereditary amyloid TTR with cardiomyopathy (ATTR-CM) and wild-type amyloid TTR (ATTRwt) amyloidosis, which result from amyloid TTR (ATTR) deposition, are difficult to distinguish due to the close similarities of symptoms. Thus, many researchers investigated the role of ATTR as a biomarker, especially its potential for differential diagnosis due to its varying pathogenic involvement in hereditary ATTR-CM and ATTRwt amyloidosis. As a result, the detection of ATTR became valuable in the diagnosis and determination of the best course of treatment for ATTR amyloidoses. Assessing the extent of ATTR deposition and genetic analysis could help in determining disease progression, and thus survival rate could be improved following the determination of the appropriate course of treatment for the patient. Here, the perspectives of ATTR in various diseases were presented.
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Ferreira, Nelson, Maria Saraiva, and Maria Almeida. "Uncovering the Neuroprotective Mechanisms of Curcumin on Transthyretin Amyloidosis." International Journal of Molecular Sciences 20, no. 6 (March 14, 2019): 1287. http://dx.doi.org/10.3390/ijms20061287.
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Transthyretin (TTR) amyloidoses (ATTR amyloidosis) are diseases associated with transthyretin (TTR) misfolding, aggregation and extracellular deposition in tissues as amyloid. Clinical manifestations of the disease are variable and include mainly polyneuropathy and/or cardiomyopathy. The reasons why TTR forms aggregates and amyloid are related with amino acid substitutions in the protein due to mutations, or with environmental alterations associated with aging, that make the protein more unstable and prone to aggregation. According to this model, several therapeutic approaches have been proposed for the diseases that range from stabilization of TTR, using chemical chaperones, to clearance of the aggregated protein deposited in tissues in the form of oligomers or small aggregates, by the action of disruptors or by activation of the immune system. Interestingly, different studies revealed that curcumin presents anti-amyloid properties, targeting multiple steps in the ATTR amyloidogenic cascade. The effects of curcumin on ATTR amyloidosis will be reviewed and discussed in the current work in order to contribute to knowledge of the molecular mechanisms involved in TTR amyloidosis and propose more efficient drugs for therapy.
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D'Souza, Anita, Keren Osman, Cristiana Costa Chase, Azah Borham, and Marianna Bruno. "The Hematologist's Role in Amyloidosis Management: Disease Awareness, Diagnostic Workup, and Practice Patterns." Blood 136, Supplement 1 (November 5, 2020): 28–29. http://dx.doi.org/10.1182/blood-2020-137740.
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Introduction: Systemic amyloidoses are progressive, life-threatening diseases characterized by the deposition of amyloid protein fibrils of varying origin in different tissues/organ systems (Merlini G, et al. N Engl J Med 2003;349:583-96). The precursor amyloidogenic protein influences the disease's clinical course, and identification of the specific protein is essential because treatment varies substantially by subtype. While there are 36 known proteins that can aggregate as amyloid in humans (Benson MD, et al. Amyloid 2018;25:215-9), the two most prevalent protein subtypes causing cardiac amyloidosis are derived from immunoglobulin light chains (AL) and transthyretin (ATTR) (Kittleson MM, et al. Circulation 2020;141:e7-22). Both AL and ATTR subtypes often infiltrate the heart, resulting in a restrictive cardiomyopathy along with other multiorgan involvement. Appropriate classification, early identification, and prompt treatment may substantially improve clinical outcomes. Because AL disease occurs in the context of plasma cell dyscrasia, hematologists can play an important role in amyloidosis suspicion, diagnostic workup, and management. However, differentiation of AL and ATTR amyloidoses in patients with signs of cardiac dysfunction is often challenging, and a multidisciplinary approach, including referral to cardiologists, is recommended early in the patient diagnostic workup. To gain insights into hematologists' disease awareness and practices, we interviewed hematologists involved in amyloidosis patient care across the US. Methods: A qualitative double-blind telephone survey was conducted between November 2019 and February 2020 of US hematologists who had diagnosed and/or treated at least 2 patients with AL amyloidosis over the past 2 years. The participants differed based on their experience in various clinical practice settings, including community hospital and private practices, academic institutions, and amyloidosis centers. Results: A total of 16 hematologists participated in the survey (community hospital, n=3; community private practice, n=5; academic institution, n=3; amyloidosis center, n=5). Hematologists at amyloidosis/academic centers (AAC) reported that the AL amyloidosis patient's journey typically involved visits to multiple primary care physicians and specialists in the community over a prolonged period (approximately 1 to 1.5 years) before the patient received a diagnosis (Figure [A]). Community specialists' referrals to academic physicians within the same specialty, due to lack of familiarity with amyloidosis centers, contributed in part to the delay. Several differences were found between hematologists in the community and those at AAC in level of disease awareness and referral/testing practices (Table; Figure [B]). Hematologists in community practice were less likely to be aware of ATTR amyloidosis, refer patients with suspected amyloid to cardiologists, or conduct recommended screening/diagnostic testing. In contrast, hematologists at AAC were highly aware of ATTR amyloidosis, collaborated closely with cardiologists, and used recommended amyloidosis tests. Across practice settings, hematologists consistently conducted biopsies of bone marrow and fat pad in patients with suspected AL amyloidosis to confirm the presence of amyloid. After amyloid was confirmed with Congo red staining, 75% of community hematologists discontinued testing, without establishing the amyloid protein subtype; hematologists at AAC consistently assessed amyloid protein subtype using immunohistochemistry and/or mass spectrometry to differentiate AL and ATTR prior to initiating treatment. Diagnostic algorithms supporting AL and ATTR differentiation were consistently in place and followed at AAC but not in community-based practices. Conclusions: Disease awareness, referral practices, and screening/testing procedures can differ between hematologists in the community setting and those in AAC. Community hematologists may benefit from additional education and wider use of diagnostic algorithms on AL/ATTR amyloidosis. Reinforcing the importance of cardiology referral and guidance on best practices for screening/biopsies/subtyping in patients with suspected amyloidosis who have cardiac symptoms should be prioritized. Disclosures D'Souza: Amgen, Merck, TenoBio: Research Funding; Akcea, Imbrium, Janssen, Pfizer: Consultancy. Costa Chase:Celgene: Speakers Bureau. Borham:Pfizer: Current Employment, Current equity holder in publicly-traded company. Bruno:Pfizer: Current Employment, Current equity holder in publicly-traded company.
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Staron, Andrew, Lawreen H. Connors, Frederick L. Ruberg, John L. Berk, Lisa M. Mendelson, and Vaishali Sanchorawala. "The Changing Face of Amyloidosis Referrals at a Tertiary Center over the Past 3 Decades." Blood 132, Supplement 1 (November 29, 2018): 5536. http://dx.doi.org/10.1182/blood-2018-99-112193.
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Abstract Amyloidosis is an increasingly recognized group of disorders, characterized by the deposition of misfolded protein aggregates in various tissues and organs. For over 50 years, the Amyloidosis Center at Boston University Medical Center (BUMC) has taken lead in the comprehensive evaluation and treatment of patients with this disease. The center serves as a tertiary referral site both nationally and globally, with patients visiting from 18 countries in recent years. Historically, immunoglobulin light chain (AL) amyloidosis associated with a plasma cell dyscrasia has had the greatest prevalence at our center. Other forms of amyloidosis, such as the hereditary mutant transthyretin (ATTRm) and age-related wild type transthyretin (ATTRwt) amyloidoses, have been seen less commonly due in part to underdiagnosis and a perceived paucity of effective treatments. We report here the spectrum of referrals at the Amyloidosis Center at BUMC from 1990 to 2017. We used data from a prospectively maintained database of consented patients. Of the 3084 patients seen for an initial evaluation at our center during this period, patients with AL amyloidosis decreased from 86% to 79% to 65% in the first, second and third decade, respectively. In the same time intervals, ATTRm amyloidosis cases increased from 12% to 14% to 19% of the total patients; an even steeper increase, from 2% to 7% to 16%, was seen in patients with ATTRwt amyloidosis. There is a marked trend towards more referrals of ATTR amyloidosis at BUMC. We believe this reflects increasing awareness and advancements in the diagnostic and therapeutic landscape of ATTR amyloidosis. In the early 2000s, the potential for misdiagnosis of hereditary ATTR as AL amyloidosis was recognized (Lachmann, et al. N Engl J Med. 2002). Accordingly, biochemical analysis by immunogold electron microscopy or laser capture tandem mass spectrometry has become a standard for more accurate typing of amyloid protein. Availability and utilization of these specific pathological modalities may in part explain the growing proportion of ATTR amyloidosis seen at our center. Perhaps an even more significant factor is the development of nuclear cardiac imaging techniques, which accurately diagnose ATTR cardiac amyloidosis without the need for endomyocardial biopsy. In the last decade, technetium associated bone-avid tracers, such as pyrophosphate (PYP), have been found to be highly sensitive and specific in identifying ATTR cardiac amyloidosis among patients with heart failure (Gillmore, et al. Circulation. 2016). Ease of performance and interpretation, availability and standardization have spurred widespread adaptation of this imaging modality, thereby allowing for recognition of ATTR cases that were undiagnosed in prior decades. A recent surge in diagnosis of ATTR amyloidosis is coincident with an evolving therapeutic landscape. There have been a number of clinical trials for ATTR amyloidosis, investigating transthyretin protein suppression and stabilization, as well as fibril clearance. Three therapies have completed phase III trials and are pending US regulatory review and registration. Publicity surrounding these trials has led physicians and patients to seek referral to tertiary centers for evaluation for novel treatments. The rise in new ATTR referrals at BUMC is countered by a decline in AL amyloidosis referrals, from a former average of 102 new cases per year to 91 per year in the last decade. We believe this to be largely owed to increasing experience with and adoption by community hematologists of the therapeutic options for AL amyloidosis, which are derived from treatments for multiple myeloma. In conclusion, once thought to be exceedingly rare, ATTR is becoming an increasingly prevalent form of amyloidosis at tertiary centers, comprising nearly 1 of every 3 new referrals at BUMC in the past decade. We anticipate that this proportion will rise further as PYP nuclear imaging becomes incorporated into screening algorithms for heart failure and awareness spreads about the anticipated approval of new pharmaceuticals for ATTR amyloidosis. Disclosures Berk: Ionis: Honoraria, Other: Investigator; Alnylam: Honoraria, Other: Investigator; Pfizer: Other: Investigator.
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Khoor, Andras, and Thomas V. Colby. "Amyloidosis of the Lung." Archives of Pathology & Laboratory Medicine 141, no. 2 (February 1, 2017): 247–54. http://dx.doi.org/10.5858/arpa.2016-0102-ra.
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Context.—Amyloidosis is a heterogeneous group of diseases characterized by the deposition of congophilic amyloid fibrils in the extracellular matrix of tissues and organs. To date, 31 fibril proteins have been identified in humans, and it is now recommended that amyloidoses be named after these fibril proteins. Based on this classification scheme, the most common forms of amyloidosis include systemic AL (formerly primary), systemic AA (formerly secondary), systemic wild-type ATTR (formerly age-related or senile systemic), and systemic hereditary ATTR amyloidosis (formerly familial amyloid polyneuropathy). Three different clinicopathologic forms of amyloidosis can be seen in the lungs: diffuse alveolar-septal amyloidosis, nodular pulmonary amyloidosis, and tracheobronchial amyloidosis. Objective.—To clarify the relationship between the fibril protein–based amyloidosis classification system and the clinicopathologic forms of pulmonary amyloidosis and to provide a useful guide for diagnosing these entities for the practicing pathologist. Data Sources.—This is a narrative review based on PubMed searches and the authors' own experiences. Conclusions.—Diffuse alveolar-septal amyloidosis is usually caused by systemic AL amyloidosis, whereas nodular pulmonary amyloidosis and tracheobronchial amyloidosis usually represent localized AL amyloidosis. However, these generalized scenarios cannot always be applied to individual cases. Because the treatment options for amyloidosis are dependent on the fibril protein–based classifications and whether the process is systemic or localized, the workup of new clinically relevant cases should include amyloid subtyping (preferably with mass spectrometry–based proteomic analysis) and further clinical investigation.
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Koike, Haruki, and Masahisa Katsuno. "The Ultrastructure of Tissue Damage by Amyloid Fibrils." Molecules 26, no. 15 (July 29, 2021): 4611. http://dx.doi.org/10.3390/molecules26154611.
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Amyloidosis is a group of diseases that includes Alzheimer’s disease, prion diseases, transthyretin (ATTR) amyloidosis, and immunoglobulin light chain (AL) amyloidosis. The mechanism of organ dysfunction resulting from amyloidosis has been a topic of debate. This review focuses on the ultrastructure of tissue damage resulting from amyloid deposition and therapeutic insights based on the pathophysiology of amyloidosis. Studies of nerve biopsy or cardiac autopsy specimens from patients with ATTR and AL amyloidoses show atrophy of cells near amyloid fibril aggregates. In addition to the stress or toxicity attributable to amyloid fibrils themselves, the toxicity of non-fibrillar states of amyloidogenic proteins, particularly oligomers, may also participate in the mechanisms of tissue damage. The obscuration of the basement and cytoplasmic membranes of cells near amyloid fibrils attributable to an affinity of components constituting these membranes to those of amyloid fibrils may also play an important role in tissue damage. Possible major therapeutic strategies based on pathophysiology of amyloidosis consist of the following: (1) reducing or preventing the production of causative proteins; (2) preventing the causative proteins from participating in the process of amyloid fibril formation; and/or (3) eliminating already-deposited amyloid fibrils. As the development of novel disease-modifying therapies such as short interfering RNA, antisense oligonucleotide, and monoclonal antibodies is remarkable, early diagnosis and appropriate selection of treatment is becoming more and more important for patients with amyloidosis.
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Yilmaz, A., J. Bauersachs, F. Bengel, R. Büchel, I. Kindermann, K. Klingel, F. Knebel, et al. "Diagnosis and treatment of cardiac amyloidosis: position statement of the German Cardiac Society (DGK)." Clinical Research in Cardiology 110, no. 4 (January 18, 2021): 479–506. http://dx.doi.org/10.1007/s00392-020-01799-3.
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AbstractSystemic forms of amyloidosis affecting the heart are mostly light-chain (AL) and transthyretin (ATTR) amyloidoses. The latter is caused by deposition of misfolded transthyretin, either in wild-type (ATTRwt) or mutant (ATTRv) conformation. For diagnostics, specific serum biomarkers and modern non-invasive imaging techniques, such as cardiovascular magnetic resonance imaging (CMR) and scintigraphic methods, are available today. These imaging techniques do not only complement conventional echocardiography, but also allow for accurate assessment of the extent of cardiac involvement, in addition to diagnosing cardiac amyloidosis. Endomyocardial biopsy still plays a major role in the histopathological diagnosis and subtyping of cardiac amyloidosis. The main objective of the diagnostic algorithm outlined in this position statement is to detect cardiac amyloidosis as reliably and early as possible, to accurately determine its extent, and to reliably identify the underlying subtype of amyloidosis, thereby enabling subsequent targeted treatment.
Dissertations / Theses on the topic "ATTR amyloidosys"
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Arvidsson, Sandra. "Cardiac function in hereditary transthyretin amyloidosis : an echocardiographic study." Doctoral thesis, Umeå universitet, Institutionen för folkhälsa och klinisk medicin, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-113891.
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Background: Hereditary transthyretin amyloidosis (ATTR) is a lethal disease in which misfolded transthyretin (TTR) proteins accumulate as insoluble aggregates in tissues throughout the body. A common mutation is the exchange of valine to methionine at place 30 (TTR V30M), a form endemically found in the northern parts of Sweden. The main treatment option for ATTR amyloidosis is liver transplantation as the procedure halts production of mutated transthyretin. The disease is associated with marked phenotypic diversity ranging from predominant cardiac complications to pure neuropathy. Two different types of fibril composition – one in which both fragmented and full-length TTR are present (type A) and one consisting of only full-length TTR (type B) have been suggested to account for some phenotypic differences. Cardiac amyloidosis is associated with increased myocardial thickness and the disease could easily be mistaken for other entities characterised by myocardial thickening, such as sarcomeric hypertrophic cardiomyopathy (HCM). The aims in this thesis were to investigate echocardiographic characteristics in Swedish ATTR amyloidosis patients, and to identify markers aiding in differentiating ATTR heart disease from HCM. Another objective was to examine the impact of fibril composition and sex on the phenotypic variation in amyloid heart disease. Methods: A total of 122 ATTR amyloidosis patients that had undergone thorough echocardiographic examinations were included in the studies. Analyses of ventricular geometry as well as assessment of systolic and diastolic function were performed, using both conventional echocardiographic methods and speckle tracking technique. ECG analysis was conducted in study I, allowing measurement of QRS voltage. In study I and study II ATTR patients were compared to patients with HCM. In addition, 30 healthy controls were added to study II. Results: When parameters from ECG and echocardiography were investigated, the results revealed that the combination of QRS voltage <30 mm (<3 mV) and an interventricular/posterior wall thickness quotient <1.6 could differentiate cardiac ATTR amyloidosis from HCM. Differences in degree of right ventricular involvement were also demonstrated between HCM and ATTR amyloidosis, where ATTR patients displayed a right ventricular apical sparing pattern whereas the inverse pattern was found in HCM. Analysis of fibril composition revealed increased LV wall thickness in type A patients compared to type B, but in addition type A women displayed both lower myocardial thickness and more preserved systolic function as compared to type A males. When cardiac geometry and function were evaluated pre and post liver transplantation in type A and B patients, significant deterioration was detected in type A but not in type B patients after liver transplantation. Conclusions: Increasing awareness of typical cardiac amyloidotic signs by echocardiography is important to reduce the risk of delayed diagnosis. Our classification model based on ECG and echocardiography could aid in differentiating ATTR amyloidosis from HCM. Furthermore, the apical sparing pattern found in the right ventricle may pose another clue for amyloid heart disease, although it requires to be studied further. Furthermore, we disclosed that type A fibrils, male sex and increasing age were important determinants of increased myocardial thickness. As type A fibril patients displayed rapid cardiac deterioration after liver transplantation other treatment options should probably be sought for this group of patients.
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Norgren, Nina. "Hereditary transthyretin amyloidosis (ATTR V30M) : from genes to genealogy." Doctoral thesis, Umeå universitet, Medicin, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-84494.
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Background: Hereditary transthyretin amyloidosis is an autosomal dominant disease with a reduced penetrance. The most common mutation in Sweden is the V30M mutation in the transthyretin gene. Clustering areas of the disease can be found in Northern Sweden, Portugal, Brazil and Japan, although sporadic cases exist worldwide. Despite being caused by the same mutation, there are large differences in onset, penetrance and symptoms of the disease. Swedish V30M patients typically have a later onset with a lower penetrance compared to those from the clustering Portuguese V30M areas. The reasons for these differences have not been fully understood. The aim of this thesis is to study mechanisms that may influence onset and symptoms and investigate why patients carrying the same mutation have different phenotypes. Methods: Genealogy studies were performed on all known V30M carriers in Sweden using standard genealogy methods. DNA samples from patients, asymptomatic carriers and controls from different countries were collected and the transthyretin gene was sequenced. Liver biopsies from patients were used for allele specific expression analysis and a cell assay was used for miRNA analysis with the mutated allele. Gene expression analysis was performed on biopsies from liver and fat from patients and controls. Results and conclusions: Genealogic analysis of all known Swedish V30M carriers managed to link together 73% of the Swedish ATTR V30M population to six different ancestors from the 17th and 18th century, thus dating the Swedish V30M mutation to be more than 400 years old. A founder effect was also visible in descendants to one of the ancestors, producing a later age at onset. Sequencing of the transthyretin gene revealed a SNP in the 3’ UTR of all Swedish V30M carriers that was not found in any of the Japanese or French V30M carriers. The SNP was present on the Swedish transthyretin haplotype and defined the Swedish V30M population as separate from others. However, the SNP itself had no effect upon phenotype or onset of disease. Gene expression analysis of liver and fat tissue revealed a change in genetic profile of the patients’ livers, in contrast to the unchanged profile of the fat tissue. A changed genetic profile of the liver could explain why domino liver recipients develop the disease much earlier than expected.
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Hossain, Ishrat. "Preparation of monoclonal antibodies against immunoglobulin kappa of AL-amyloidosis and characterization of antibody producing hybridoma cells." Thesis, Uppsala universitet, Institutionen för kvinnors och barns hälsa, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-334412.
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Ihse, Elisabet. "Two Types of Fibrils in ATTR Amyloidosis : Implications for Clinical Phenotype and Treatment Outcome." Doctoral thesis, Uppsala universitet, Molekylär och morfologisk patologi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-160980.
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Systemic amyloidoses are a group of lethal diseases where proteins aggregate into fibrillar structures, called amyloid fibrils, that deposits throughout the body. Transthyretin (TTR) causes one type of amyloidosis, in which the aggregates mainly infiltrate nervous and cardiac tissue. Almost a hundred different mutations in the TTR gene are known to trigger the disease, but wild-type (wt) TTR is also incorporated into the fibrils, and may alone form amyloid. Patients with the TTRV30M mutation show, for unknown reasons, two clinical phenotypes. Some have an early onset of disease without cardiomyopathy while others have a late onset and cardiomyopathy. It has previously been described that amyloid fibrils formed from TTRV30M can have two different compositions; either with truncated molecules beside full-length TTR (type A) or only-full-length molecules (type B). In this thesis, the clinical importance of the two types of amyloid fibrils was investigated. We found that the fibril composition types are correlated to the two clinical phenotypes seen among TTRV30M patients, with type A fibrils present in late onset patients and type B fibrils in early onset patients. The only treatment for hereditary TTR amyloidosis has been liver transplantation, whereby the liver producing the mutant TTR is replaced by an organ only producing wt protein. However, in some patients, cardiac symptoms progress post-transplantationally. We demonstrated that the propensity to incorporate wtTTR differs between fibril types and tissue types in TTRV30M patients, with cardiac amyloid of type A having the highest tendency. This offers an explanation to why particularly cardiac amyloidosis develops after transplantation, and suggests which patients that are at risk for such development. By examining patients with other mutations than TTRV30M, we showed that, in contrast to the general belief, a fibril composition with truncated TTR is very common and might even be the general rule. This may explain why TTRV30M patients often have a better outcome after liver transplantation than patients with other mutations. In conclusion, this thesis has contributed with one piece to the puzzle of understanding the differences in clinical phenotype and treatment response between TTR amyloidosis patients, by demonstrating corresponding differences at a molecular level.
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f, cappelli. "Prevalence and prognostic implication of arrhythmic burden in TTR amyloidosis." Doctoral thesis, 2022. https://hdl.handle.net/2158/1263717.
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Giadone, Richard Michael. "Defining cellular and molecular mechanisms of hereditary transthyretin amyloidosis." Thesis, 2020. https://hdl.handle.net/2144/41107.
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Hereditary transthyretin amyloidosis (ATTR amyloidosis) is a multi-system protein folding disorder that results from >100 described mutations in the transthyretin (TTR) gene. In the disease, non-natively folded TTR, originally produced by the liver, travels throughout circulation and deposits extracellularly at downstream target organs. The multi-tissue etiology of the disease makes it difficult to study in vitro, while no mouse model accurately recapitulates disease pathology. Therefore, we utilized patient-specific induced pluripotent stem cells (iPSCs) to test the hypothesis that production of and exposure to destabilized TTRs results in distinct cellular and molecular changes.
The liver’s contribution to the deposition of TTR at distal tissues is understudied. As a result, in Aim 1 we sought to assess the effects of destabilized TTR production on effector hepatic cells. To this end, we utilized gene editing to generate isogenic, patient iPSCs expressing either mutant or wild-type TTR. Combining this tool with single cell RNAseq, we identified hepatic proteostasis factors, including unfolded protein response (UPR) pathways, whose expression coincided with the production of destabilized TTR. Enhancing endoplasmic reticulum (ER) proteostasis within patient hepatic cells via exogenous activation of adaptive UPR signaling, we demonstrated preferential reduction in the secretion of pathogenic TTR. In turn, we demonstrated that production of disease-associated TTR correlates with expression of proteostasis factors capable of regulating TTR secretion and in turn downstream pathogenesis.
ATTR amyloidosis patients exhibit extreme phenotypic variation (e.g. TTR fibril deposits at cardiac tissue and/or peripheral nerves). In Aim 2, we sought to define responses of target cell types to pathologically-diverse TTRs. To accomplish this, we profiled transcriptomic changes resulting from exposure to a variety of destabilized TTRs to determine 1) target cell response to TTR exposure and 2) how this response changes across diverse variants and cell types. In doing so, we found that TTR exposure elicits distinct variant- and cell type-specific transcriptional responses.
Herein, we addressed our central hypothesis by profiling destabilized TTR production within hepatic cells and TTR exposure at target cell types. Collectively, these data may result in the discovery of unidentified and potentially druggable pathologically-associated pathways for ATTR amyloidosis and other systemic amyloid diseases.
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Teixeira, Cristina Alexandra Pereira. "The contribution of an animal model for the pathogenetic characterization and therapeutic approaches in ATTR cardiac amyloidosis." Doctoral thesis, 2021. https://hdl.handle.net/10216/133876.
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Teixeira, Cristina Alexandra Pereira. "The contribution of an animal model for the pathogenetic characterization and therapeutic approaches in ATTR cardiac amyloidosis." Tese, 2021. https://hdl.handle.net/10216/133876.
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Coelho, Maria Teresa Pardal Monteiro. "Disease modifying therapies for attr amyloidoses: clinical development of new drugs and impact on the natural history of the disease." Doctoral thesis, 2019. https://hdl.handle.net/10216/121905.
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Coelho, Maria Teresa Pardal Monteiro. "Disease modifying therapies for attr amyloidoses: clinical development of new drugs and impact on the natural history of the disease." Tese, 2019. https://hdl.handle.net/10216/121905.
Full textBook chapters on the topic "ATTR amyloidosys"
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Zeldenrust, Steven R. "ATTR: Diagnosis, Prognosis, and Treatment." In Amyloidosis, 191–204. Totowa, NJ: Humana Press, 2010. http://dx.doi.org/10.1007/978-1-60761-631-3_14.
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Simões, Kelma Macedo Pohlmann, and Mário Martins dos Santos Motta. "Ophthalmological Manifestations in AL and Wild-Type ATTR Amyloidosis." In Amyloidosis and Fabry Disease, 93–95. Cham: Springer International Publishing, 2023. http://dx.doi.org/10.1007/978-3-031-17759-0_9.
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Crelier, Viviane Tavares Carvalho, Fábio de Souza, and Caroline Bittar Braune. "Neurological Manifestations in AL and Wild-Type ATTR Amyloidosis." In Amyloidosis and Fabry Disease, 19–24. Cham: Springer International Publishing, 2023. http://dx.doi.org/10.1007/978-3-031-17759-0_3.
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Dias, Anelise, Giovanna Provenzano, and Raul N. G. Vianna. "Ophthalmological Manifestations in ATTRv Amyloidosis." In Amyloidosis and Fabry Disease, 83–91. Cham: Springer International Publishing, 2023. http://dx.doi.org/10.1007/978-3-031-17759-0_8.
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Nascimento, Osvaldo J. M., Wilson Marques, Pedro Tomaselli, and Carolina Lavigne-Moreira. "Neurological Manifestations in ATTRv Amyloidosis." In Amyloidosis and Fabry Disease, 5–17. Cham: Springer International Publishing, 2023. http://dx.doi.org/10.1007/978-3-031-17759-0_2.
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Couto, Raquel Germer Toja, Ana Flávia Malheiros Torbey, and Aurea Lucia Alves de Azevedo Grippa de Souza. "Clinical and Genetic Screening in ATTR and Fabry Disease in Children and Adolescents." In Amyloidosis and Fabry Disease, 423–30. Cham: Springer International Publishing, 2023. http://dx.doi.org/10.1007/978-3-031-17759-0_36.
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Aprile, C., G. Merlini, R. Saponaro, G. Cannizzaro, G. Calsamiglia, E. Anesi, and P. Garini. "Aprotinin 99mTc Myocardial Scan: Risk Stratification of Cardiac Events in Patients with Al/Attr Amyloidosis." In Radioactive Isotopes in Clinical Medicine and Research XXIII, 479–82. Basel: Birkhäuser Basel, 1999. http://dx.doi.org/10.1007/978-3-0348-8782-3_81.
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"ATTR Amyloidosis." In Diagnostic Pathology: Kidney Diseases, 254–57. Elsevier, 2016. http://dx.doi.org/10.1016/b978-0-323-37707-2.50051-3.
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Grogan, Martha. "Cardiac amyloidosis." In ESC CardioMed, 1545–49. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198784906.003.0373.
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Cardiac amyloidosis is an important cause of heart failure and cardiac arrhythmias, yet cardiologists often miss the diagnosis. Immunoglobulin light-chain amyloidosis (AL) is relatively rare, but likely underdiagnosed. The median survival of untreated patients with cardiac AL is 6 months after the onset of heart failure, highlighting the importance of early diagnosis. Wild-type transthyretin amyloidosis (ATTR) is increasingly recognized, especially in males over the age of 60 years. Although the clinical course of wild-type ATTR is more indolent, the median survival is approximately 3.5 years from diagnosis. Typical echocardiographic findings of increased left and right ventricular wall thickness, diastolic dysfunction, and pericardial effusion may suggest cardiac amyloidosis, along with abnormal delayed gadolinium enhancement and difficulty nulling the myocardium on cardiac magnetic resonance imaging. For AL, a tissue diagnosis is required. In contrast, ATTR may be diagnosed non-invasively with grade 2/3 uptake by nuclear scintigraphy in the absence of a monoclonal protein. Treatment of cardiac amyloidosis is entirely dependent on the type of amyloid and is directed at the underlying precursor protein or disrupting existing deposits. Cardiac care is supportive and challenging. Standard heart failure medications such as beta blockers and angiotensin-converting enzyme inhibitors are not routinely indicated and often cause haemodynamic deterioration. Outcomes of source-directed therapy for AL are improving and several clinical trials of treatment for ATTR are ongoing.
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Fuchs, Tobias A., and Oliver Gaemperli. "Infiltrative disease (amyloidosis/sarcoidosis)." In ESC CardioMed, edited by Philipp Kaufmann, 605–8. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198784906.003.0128_update_001.
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Infiltrative cardiomyopathies such as sarcoidosis and amyloidosis are characterized by interstitial deposition of pathological acellular or cellular tissue within the myocardium. Nuclear cardiac imaging plays an important role in the assessment of infiltrative cardiac disease through direct visualization of infiltrative substrates or inflammation, or both, by radiolabelled compounds. Cardiac involvement from sarcoidosis is rather common, and appears to worsen the overall prognosis of the disease. Radionuclide imaging using 18F-fluorodeoxyglucose (FDG) positron emission tomography is a very sensitive method to detect cardiac sarcoidosis. Most importantly, it allows detecting early inflammatory stages previous to any morphological changes such as fibrosis or scar and thereby facilitates early preventive treatment. In order to suppress physiological FDG uptake and obtain good image quality, meticulous patient preparation including prolonged fasting, diet, and heparin load prior to FDG imaging is recommended. Cardiac amyloidosis is an infiltrative cardiomyopathy characterized by interstitial deposits of amyloid that can be visualized by scintigraphy using molecular-targeted radiolabelled compounds such as 99mTc-labelled pyrophosphate or 3,3-diphosphono-1,2-propanodicarboxylic acid. Because of the high sensitivity for transthyretin-type (ATTR) amyloidosis, scintigraphy may help to phenotype cardiac amyloidosis and separate ATTR from light-chain amyloidosis.
Conference papers on the topic "ATTR amyloidosys"
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Azevedo, Fernanda Reis de, Michael Polydefkis, Simina Ticau, David Erbe, Anastasia McManus, Emre Aldinc, David Adams, Mary Reilly, Akshay Vaishnaw, and Paul Nio. "Neurofilament Light Chain (NfL) as a Potential Biomarker of Treatment Response in Hereditary TransthyretinMediated (hATTR) Amyloidosis: Patisiran Global OLE Study." In XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.200.
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Introduction: Patisiran is approved for the treatment of hATTR amyloidosis with polyneuropathy and its long-term efficacy/safety is being studied in a Global OLE. Plasma biomarkers are being investigated for utility in facilitating earlier diagnosis and monitoring disease /treatment response. Objective: Evaluate long-term change in neurofilament light chain (NfL) levels in response to patisiran in patients enrolled in the Global Open-Label Extension (OLE) study. Methods: NfL plasma levels were measured in duplicate in healthy controls and patients with ATTRv amyloidosis with polyneuropathy using the Quanterix Simoa platform. Patient samples were analyzed from the APOLLO study at baseline and 18 months, and also measured at 12 and 24 months following APOLLO in patients who rolled into the Global OLE. Results: NfL levels at APOLLO baseline were 63.2 (placebo) and 72.1 pg/ mL (patisiran). NfL increased during APOLLO in the placebo group (99.5 pg/mL), whereas a significant decrease was observed at 18 months following patisiran (48.8 pg/mL). Reduced NfL levels were maintained in the APOLLO-patisiran group through 24 months of additional patisiran treatment in the Global OLE (44.0 pg/mL), consistent with maintained improvement in mNIS+7. Upon initiation of patisiran in the Global OLE, the APOLLO-placebo group experienced a reduction in NfL levels through 24 months (44.2 pg/mL), reaching a similar level to the APOLLO-patisiran group. Conclusions: NfL may serve as a biomarker of active nerve damage and polyneuropathy, making it useful as a potential biomarker of disease progression, treatment response and for earlier diagnosis of polyneuropathy in patients with ATTRv amyloidosis and monitoring disease.
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Carroll, Antonia, Cindy Lin, Susanna Park, Neil Simon, Mary Reilly, Steve Vucic, and Matthew Kiernan. "036 Nerve excitability and motor unit number estimation: early biomarkers of nerve involvement in hereditary amyloidosis (ATTRv)." In ANZAN Annual Scientific Meeting 2021 Abstracts. BMJ Publishing Group Ltd, 2021. http://dx.doi.org/10.1136/bmjno-2021-anzan.36.
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