Emerging therapies in transthyretin amyloidosis  – a new wave of hope after years of stagnancy?

Transthyretin amyloidosis (ATTR) is a rare, yet underdiagnosed disease characterized by progressive impairment of neurologic and cardiac function due to deposition of misfolded transthyretin. Despite great efforts, such as the introduction of orthotopic liver transplant, the devastating prognosis for both variant and wild ‐type ATTR patients remained unchanged over the last decades, mainly due to a lack of specific therapies. Fortunately, recent years saw the introduction of promising targeted therapies, which aim to interfere with the deposition of misfolded transthyretin (TTR) at various stages of the cascade und erlying ATTR progression. These include TTR tetramer stabilizers (tafamidis, diflunisal, epigallocatechin‐3‐gallate), TTR silencers (inotersen, patisiran) and fibril disruptors (monoclonal antibodies, doxycycline and tauroursodeoxycholic acid). In the context of this review we explain their mech anisms of action, analyse their efficacy on neurologic and cardiac function based on all clinical trials conducted to date and discuss their clinical applicability. Eventually suggestions for future clinical research into the field are provided.
Source: European Journal of Heart Failure - Category: Cardiology Authors: Tags: Review Source Type: research

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Authors: Kristen AV Abstract Cardiac amyloidosis is a heterogeneous group of diseases characterized by extracellular deposition of amyloid fibrils in many different organs finally resulting in organ failure. Cardiac involvement is common for immunoglobulin light chain amyloidosis (AL) or transthyretin amyloidosis (ATTR); the latter is caused by a transthyretin gene variant or wild-type protein. Precise diagnostic assessment including laboratory tests, electrocardiography, echocardiography, cardiac magnetic resonance imaging, biopsy, and/or bone scintigraphy is mandatory for definition of the amyloid type ...
Source: Herz - Category: Cardiology Tags: Herz Source Type: research
Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
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Conclusion: Tafamidis is an effective and safe oral medication for the treatment of the cardiomyopathy of transthyretin-mediated amyloidosis in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization. PMID: 31735059 [PubMed - as supplied by publisher]
Source: The Annals of Pharmacotherapy - Category: Drugs & Pharmacology Authors: Tags: Ann Pharmacother Source Type: research
In conclusion, we show here that sEVs are responsible for mediating paracrine senescence and speculate that they could be involved in inducing bystander senescence during therapy-induced senescence or aging. In fact, when compared to soluble factors, sEVs have different biophysical and biochemical properties as they have a longer lifespan than do soluble factors and they are more resistant to protease degradation. The idea that blocking sEV secretion could be a potential therapeutic approach to alleviate senescence "spreading" during chemotherapy-induced senescence or in aging tissues presents itself as a very at...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Systemic amyloidosis is a rare condition that can manifest with cardiomyopathy, hepatic dysfunction, and renal disease. Diagnosis is often missed and/or delayed due to chronic multi ‐system involvement and indeterminate signs and symptoms. Treatment generally involves systemic therapy and autologous stem‐cell transplantation. AbstractSystemic amyloidosis is a rare condition that can manifest with cardiomyopathy, hepatic dysfunction, and renal disease. Diagnosis is often missed and/or delayed due to chronic multi ‐system involvement and indeterminate signs and symptoms. Treatment generally involves systemic therapy an...
Source: Clinical Case Reports - Category: General Medicine Authors: Tags: CASE REPORT Source Type: research
In conclusion, there is solid evidence that obesity deregulates cellular mechanisms related to nutrient sensing. Altered Intercellular Communication It is accepted that aging impacts the organism at the cellular level, but also decreases the capacity of cells of an organism to interact. During aging, there is a decreased communication at the neuronal, neuroendocrine, and endocrine levels. Two of the most compelling examples of impaired communication are inflammaging and immunosenescence. The inflammaging phenotype results in elevated cytokines. These cytokines can accelerate and propagate the aging process. T...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In this study, we report the age-associated differences between fetal MSC (fMSC) populations and MSCs isolated from elderly donors with respect to their transcriptomes. We successfully reprogrammed fMSCs (55 days post conception) and adult MSC (aMSC; 60-74 years) to iPSCs and, subsequently, generated the corresponding iMSCs. In addition, iMSCs were also derived from ESCs. The iMSCs were similar although not identical to primary MSCs. We unraveled a putative rejuvenation and aging gene expression signature. We show that iMSCs irrespective of donor age and cell type re-acquired a similar secretome to that of th...
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Conclusions: In newly diagnosed systemic AL amyloidosis, doxycycline was safe with concurrent chemotherapy. The low 1-year early mortality of 20% and autologous stem cell transplant rate of 60% compares favorably to prior reports. These findings warrant a randomized, multicenter study.DisclosuresD'Souza: Prothena: Consultancy, Research Funding; Merck: Research Funding; Takeda: Research Funding; Amgen: Research Funding; Celgene: Research Funding. Dhakal: Celgene: Consultancy, Honoraria; Takeda: Honoraria, Research Funding; Amgen: Honoraria. Hari: Janssen: Honoraria; Amgen Inc.: Research Funding; Spectrum: Consultancy, Resea...
Source: Blood - Category: Hematology Authors: Tags: 653. Myeloma: Therapy, excluding Transplantation: Poster I Source Type: research
Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more. This content is...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more. This content is...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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