Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.25.1 (proteasome)
 28,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Systemic amyloidosis of the immunoglobulin light-chain (AL) or transthyretin type (ATTR) is a multisystem protein deposition disease that often involves the heart. Delays in diagnosis are very common and can have detrimental consequences on patient outcomes. Because both major types can now be distinguished quickly and treated effectively, clear approaches are required. There have been advances in radioisotope scintigraphy, monoclonal protein testing and mass spectrometry for typing that need coordinated application. We have entered an era in which rapid diagnosis and ready therapy will save lives, therefore we must develop coherent approaches to this multisystem disease. The prognosis for AL has improved significantly with the incorporation of novel agents such as proteasome inhibitors, immunomodulators and monoclonal antibodies against plasma cells. Multiple independent studies have demonstrated the efficacy of these agents in AL, though tolerability can become an issue with dose reductions required in many cases. Median overall survival for patients achieving complete responses after stem cell transplant and consolidation exceeds a decade. The prognosis for ATTR, both age-related wild-type (ATTRwt) and hereditary due to variants of transthyretin (ATTRv), has improved as well due to the availability of the stabilizer tafamidis and the RNA-interference agents patisiran and inotersen. In both AL and ATTR, with elimination or suppression of the pathologic amyloid-forming protein, symptomatic involvement of the heart, kidneys and peripheral nervous system can improve as well. In this review, we present the current state of diagnosing and treating the two major types of systemic amyloidosis, emphasizing the coherent clinical application of the new tools and treatments. Implementation of the approaches we provide will enable rapid identification of amyloid type and rational selection of therapy.
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PMID:The diagnostic challenges of cardiac amyloidosis: A practical approach to the two main types. 3261 4

Systemic amyloidosis is a heterogeneous group of diseases associated with protein misfolding into insoluble beta-sheet rich structures that deposit extracellularly in different organs, eventually compromising their function. There are more than 30 different proteins, known to be amyloidogenic with “light chain” (AL)-amyloidosis being the most common type, followed by transthyretin (ATTR)-, and amyloid protein A (AA)-amyloidosis. Systemic amyloidosis is a rare disease with an incidence of around 10 patients in 1 million inhabitants. Recently several new therapeutic options have been developed for subgroups of amyloidosis patients, and the introduction of novel therapies for plasma cell myeloma has led to an increase in the therapeutic armamentarium for plasma cell disorders, including AL amyloidosis. Among them, proteasome inhibitors, immunomodulatory agents (-imids), and monoclonal antibodies have been successfully introduced into clinical practice. Still, high-quality data from randomised controlled trials regarding the benefit of these cost-intensive drugs in AL amyloidosis are widely lacking, and due to the rarity of the disease many physicians will not gain routine experience in the management of these frail patients. The diagnosis of AL amyloidosis relies on a close collaboration between clinicians, pathologists, imaging experts, and sometimes geneticists. Diagnosis and treatment options in this complex disorder should be discussed in dedicated multidisciplinary boards. In January 2020, the first meeting of the Swiss Amyloidosis Network took place in Zurich, Switzerland. One aim of this meeting was to establish a consensus guideline regarding the diagnostic work-up and the treatment recommendations for systemic amyloidosis tailored to the Swiss health care system. Forty-five participants from different fields in medicine discussed many aspects of amyloidosis. These are the Swiss Amyloidosis Network recommendations which focus on diagnostic work-up and treatment of AL-amyloidosis.
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PMID:Expert recommendation from the Swiss Amyloidosis Network (SAN) for systemic AL-amyloidosis. 3327 11