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- W2556936900 abstract "Some TTR mutants target the central nervous system (CNS). Familial amyloid polyneuropathy (FAP) with leptomeningeal involvement has been described in 9% of transthyretin (TTR) mutations and in valine for methionine at position 30 (V30M) patients. These individuals present dementia, ataxia, brain hemorrhages and focal neurological episodes (FNEs). FNEs occurred also in V30M FAP patients with longer disease duration, who have undergone liver transplant to remove the source of plasma mutant TTR as a form of treatment. It is thus to expect that as better treatments for FAP emerge and prolong survival, meningeal-vascular CNS deposition will increase and need special therapies. Recently, we detected TTR meningeal-vascular deposition in a V30M TTR transgenic mouse model, opening new avenues of research to investigate selective treatments of this condition. Since pre-clinical studies with TTR siRNA therapeutics were shown to promote clearance of TTR non-fibrillar deposits in several organs and tissues, we investigated its effect on TTR meningeal-vascular deposition. We show that systemically administered TTR siRNA promoted TTR clearance in the extracellular matrix of meninges and brain blood vessels. Surprisingly, despite the striking decline of blood TTR, cerebrospinal fluid TTR levels were unaffected. Though this is reassuring because siRNA will not interfere with the neuroprotective role of TTR in the CNS, it raises new questions on therapeutical approaches for CNS ATTR." @default.
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- W2556936900 date "2016-10-01" @default.
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- W2556936900 title "Efficiency of silencing RNA for removal of transthyretin V30M in a TTR leptomeningeal animal model" @default.
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- W2556936900 doi "https://doi.org/10.1080/13506129.2016.1256282" @default.
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