Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
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Proteomics is routinely used to type clinical amyloid deposits, and offers additional benefit of identifying genetic variants, which can be diagnostically useful. Reviewing the proteomics data for ATTR patients attending our Centre revealed an unusually large number of samples containing a rare pathogenic H90D TTR variant alongside the more common H90N variant. ⋯ In the absence of genetic data, the identification of H90D TTR in stored tissue by proteomics should be treated with caution.
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Each monoclonal antibody light chain associated with AL amyloidosis has a unique sequence. Defining how these sequences drive amyloid deposition could facilitate faster diagnosis and lead to new treatments. ⋯ Rarely-observed light chain variable genes may carry a high risk of AL amyloidosis. New approaches are needed to define sequence-associated risk factors for AL amyloidosis. AL-Base is a foundational resource for such studies.
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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.