Tafamidis delays disease progression in patients with early stage transthyretin familial amyloid polyneuropathy: additional supportive analyses from the pivotal trial

Keohane, Denis; Schwartz, Jeffrey H.; Gundapaneni, Balarama; Stewart, Michelle; Amass, Leslie

doi:10.1080/13506129.2017.1301419

Cited by 50 publications

(39 citation statements)

References 22 publications

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“…Previous studies also reported improvements over the long term after LT in the mPND score, sensory and motor disturbances of some patients [18], and tissue-deposited amyloid regression has also been described [19,36]. Tafamidis, a transthyretin stabilizer, has been shown to delay disease progression during an 18month, double-blind, placebo-controlled randomized trial, including 128 early affected patients with hATTR V30M [23,37]. Long-term effects of tafamidis therapy demonstrated good tolerability and persistent reduction in the disease progression rate [24,25].…”

Section: Discussionmentioning

confidence: 91%

“…Tafamidis, a transthyretin stabilizer, has been shown to delay disease progression during an 18‐month, double‐blind, placebo‐controlled randomized trial, including 128 early affected patients with hATTR V30M . Long‐term effects of tafamidis therapy demonstrated good tolerability and persistent reduction in the disease progression rate .…”

Section: Discussionmentioning

confidence: 99%

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Hereditary amyloidosis related to transthyretin V30M: disease progression in treated and untreated patients

Conceição

Miranda

Castro

et al. 2018

Euro J of Neurology

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Hereditary amyloidosis related to transthyretin V30M: disease progression in treated and untreated patients

Conceição

Miranda

Castro

et al. 2018

Euro J of Neurology

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“…The administration of 'pharmacological chaperones', which stabilize the native conformation of a mutant enzyme and thus shift the folding balance away from degradation and aggregation, is being used in a clinical trial for lysosomal storage diseases (NCT00433147). Similarly, small molecules that stabilize the folded, functional state of a protein are being used in clinical trials to misassemble toxic amyloid aggregates 174 . Proteostasis can also be regulated by altering the composition of the chaperone network using small interfering RNAs (siRNAs) or compounds such as diltiazem and verapamil, both of which are Ca 2+ channel blockers, to decrease intracytoplasmic Ca 2+ levels.…”

Section: Targets and Therapeutic Interventions For Insufficient Protementioning

confidence: 99%

Emerging therapies for idiopathic pulmonary fibrosis, a progressive age-related disease

Mora

Rojas

Pardo

et al. 2017

Nat Rev Drug Discov

280

212

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Idiopathic pulmonary fibrosis (IPF) is a fatal age-associated disease that is characterized by progressive and irreversible scarring of the lung. The pathogenesis of IPF is not completely understood and current therapies are limited to those that reduce the rate of functional decline in patients with mild-to-moderate disease. In this context, new therapeutic approaches that substantially improve the survival time and quality of life of these patients are urgently needed. Our incomplete understanding of the pathogenic mechanisms of IPF and the lack of appropriate experimental models that reproduce the key characteristics of the human disease are major challenges. As ageing is a major risk factor for IPF, age-related cell perturbations such as telomere attrition, senescence, epigenetic drift, stem cell exhaustion, loss of proteostasis and mitochondrial dysfunction are becoming targets of interest for IPF therapy. In this Review, we discuss current and emerging therapies for IPF, particularly those targeting age-related mechanisms, and discuss future therapeutic approaches.Fibrosis as a pathogenic mechanism occurs in numerous organs and diseases. Fibrosis results from abnormal tissue repair and is associated with persistent and/or severe tissue damage and cellular stress. Epithelial and/or endothelial injury caused by various insults triggers interrelated wound-healing pathways to restore homeostasis 1 . Failure to adequately contain or eliminate inciting factors can exacerbate inflammation and chronic woundCorrespondence to A.L.M. anamora@pitt.edu. Competing interests statementThe authors declare competing interests: see Web version for details. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript healing responses, resulting in continued tissue damage and inadequate regeneration and, ultimately, fibrosis 2 . Although their aetiology and causative mechanisms differ, the various fibrotic diseases all have abnormal and exaggerated accumulation of extracellular matrix (ECM) components, mainly fibrillar collagens. The resulting fibrosis disturbs the normal architecture of affected organs, which ultimately leads to their dysfunction and failure. Nearly 45% of deaths in the developed world are attributable to some type of chronic fibroproliferative disease, including idiopathic pulmonary fibrosis (IPF) and end-stage fibrotic liver, kidney and heart disease 2 . The progressive nature of these diseases and the absence of effective treatments mean that a better understanding of the cellular and molecular mechanisms that contribute to the development of fibrosis is needed.Although IPF was originally thought to be an inflammation-driven disorder, clinical trials with a combination of anti-inflammatory drugs (prednisone, azathioprine and N-acetyl-Lcysteine (NAC)), failed to improve outcomes and instead increased mortality 3 . In 2014, two drugs, pirfenidone, a drug with poorly understood mechanisms, and nintedanib, a tyrosine kinase inhibitor, were approved for the treatment of IPF ...

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“…This type of evidence nourishes disease awareness, avoiding/reducing misdiagnosis of the disease [11], which can delay disease-modifying treatments, all more effective in early disease stages [9,12]. This study aims to estimate the incidence and prevalence of TTR-FAP in Portugal and to describe patients' demographic characteristics.…”

Section: Introductionmentioning

confidence: 99%

Epidemiology of Transthyretin Familial Amyloid Polyneuropathy in Portugal: A Nationwide Study

et al. 2018

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Background: Transthyretin-associated familial amyloid polyneuropathy (TTR-FAP) is a rare, hereditary, progressive and neurodegenerative disease. We aimed to study TTR-FAP epidemiology in Portugal. Methods: National, observational, prospective and retrospective, case identification of adults with TTR-FAP. Countrywide patient multiple identification sources included reference centers registries and centralized medical electronic prescription database. Crude rates were reported per 100,000 adult inhabitants. Results: Over 2010–2016 period, mean incidence rates was 0.87/100,000 (95% CI 0.68–1.10) corresponding to 71 new patients yearly, that has decreased 31% in the last 7 years. The proportion of late-onset cases (age ≥50 years) among incident cases was 28.7%. Estimated crude 2016 prevalence was 22.93/100,000 adult inhabitants (95% CI 21.90–23.99) corresponding to 1,865 TTR-FAP individuals in Portugal (45.8% male; mean age: 52.3 ± 15.4 years). In 2016, the Portuguese region with the highest TTR-FAP prevalence shows a 16% prevalence increase over the last 25 years. Conclusions: In Portugal, TTR-FAP affects both genders and mainly young adults. TTR-FAP incidence appears to be decreasing while prevalence is increasing. In comparison to previous studies, there is an increased representativeness of late-onset patients. This epidemiological setting poses future and complex challenges for the social and healthcare system, strengthening the relevance of regular epidemiologic surveillance.

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Tafamidis delays disease progression in patients with early stage transthyretin familial amyloid polyneuropathy: additional supportive analyses from the pivotal trial

Abstract: NCT00409175.

Cited by 50 publications

References 22 publications

Hereditary amyloidosis related to transthyretin V30M: disease progression in treated and untreated patients

Hereditary amyloidosis related to transthyretin V30M: disease progression in treated and untreated patients

Emerging therapies for idiopathic pulmonary fibrosis, a progressive age-related disease

Epidemiology of Transthyretin Familial Amyloid Polyneuropathy in Portugal: A Nationwide Study

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