Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
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The clinical efficacy of transthyretin (TTR) tetramer stabilisers and TTR gene silencers in addition to liver transplantation has been established for hereditary ATTR (ATTRv) amyloidosis. Accordingly, non-central nervous system (CNS) systemic amyloidosis manifestations, such as peripheral neuropathy and cardiomyopathy, are now being overcome. However, emerging disease-modifying therapeutics have limited effects on CNS amyloidosis since they target the blood-circulating TTR produced in the liver, and not the cerebral spinal fluid (CSF) TTR synthesised in the choroid plexus. ⋯ V50M) variant. Treatment-wise, blood-brain barrier-permeable stabilisers, intrathecal injection of silencers, and monoclonal antibodies against misfolded TTR and/or ATTR amyloid may potentially ameliorate CNS ATTR amyloidosis. The development of novel imaging/CSF biomarkers and disease-modifying therapies are the greatest unmet medical need in ATTRv amyloidosis and require further clinical trials.