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Journal Article
Review
Inotersen for the treatment of adults with polyneuropathy caused by hereditary transthyretin-mediated amyloidosis.
Expert Review of Clinical Pharmacology 2019 August
Introduction : Hereditary transthyretin-mediated amyloidosis (ATTRv; v for variant) is an underdiagnosed, progressive, and fatal multisystemic disease with a heterogenous clinical phenotype that is caused by TTR gene mutations that destabilize the TTR protein, resulting in its misfolding, aggregation, and deposition in tissues throughout the body. Areas covered : Inotersen, an antisense oligonucleotide inhibitor, was recently approved in the United States and Europe for the treatment of the polyneuropathy of ATTRv based on the positive results obtained in the pivotal phase 3 trial, NEURO-TTR. This review will discuss the mechanism of action of inotersen and its pharmacology, clinical efficacy, and safety and tolerability. A PubMed search using the terms 'inotersen,' 'AG10,' 'antisense oligonucleotide,' 'hereditary transthyretin amyloidosis,' 'familial amyloid polyneuropathy,' and 'familial amyloid cardiomyopathy' was performed, and the results were screened for the most relevant English language publications. The bibliographies of all retrieved articles were manually searched to identify additional studies of relevance. Expert opinion : Inotersen targets the disease-forming protein, TTR, and has been shown to improve quality of life and neuropathy progression in patients with stage 1 or 2 ATTRv with polyneuropathy. Inotersen is well tolerated, with a manageable safety profile through regular monitoring for the development of glomerulonephritis or thrombocytopenia.
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