Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
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Randomized Controlled Trial Clinical Trial
New device technologies for subcutaneous fat biopsy.
Subcutaneous fat biopsy is useful for the evaluation of amyloidosis, environmental contaminants, lipid metabolism, genetic studies and diabetes research. The present study examined new technologies for fat biopsy. ⋯ Subcutaneous fat biopsy by needle aspiration can be facilely achieved with new aspiration syringe technologies with improved needle control and enhanced patient safety.
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Transthyretin (TTR)-associated amyloidosis is a late-onset autosomal-dominant genetic disease. Over 100 amyloidogenic mutations have been identified in TTR which destabilize the TTR tetramer thereby inducing the formation of amyloid fibrils in tissues such as the heart and peripheral nerves. This disease mainly affects peripheral nerves, causing familial amyloid polyneuropathy (FAP) or heart, causing familial amyloid cardiomyopathy (FAC). ⋯ As expected, treatment with ISIS-TTR(Rx) also produced a significant decrease in plasma RBP4 levels that correlated with reductions in TTR levels. ISIS-TTR(Rx) treatment was well tolerated in both rodents and monkeys and produced a PK/PD profile consistent with prior experiences using this chemistry platform. ISIS-TTR(Rx) is currently under evaluation in a Phase 1 clinical trial in normal healthy volunteers, and interim results of this trial will be presented.
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Randomized Controlled Trial
The Diflunisal Trial: study accrual and drug tolerance.
Familial amyloidotic polyneuropathy (FAP) is a protein folding disorder that induces neuropathy and cardiomyopathy, leading to death within 7-15 years after onset of clinical disease. In vitro, small ligands binding the thyroid hormone docking site stabilize tetrameric transthyretin, inhibiting amyloid fibril formation. ⋯ To date, few recognized complications of NSAIDs have occurred in the study cohort. Data collection will be completed by November 2012.
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RNA interference (RNAi) is a sequence-specific gene-silencing mechanism triggered by double-stranded RNA and powerful tools for a gene function study and RNAi therapy. Although siRNAs offer several advantages as potential new drugs to treat various diseases, the efficient delivery system of siRNAs in vivo remains a crucial challenge for achieving the desired RNAi effect in clinical development. In particular, when considering the siRNA therapeutics for familial amyloidotic polyneuropathy (FAP) caused by the deposition of variant transthyretin (TTR) in various organs, hepatocyte-selective siRNA delivery is desired because TTR is predominantly synthesized by hepatocytes. In this study, to reveal the potential use of lactosylated dendrimer (G3)/α-cyclodextrin conjugate (Lac-α-CDE (G3)) as novel hepatocyte-selective siRNA carriers in order to treat FAP, we evaluated the RNAi effect of siRNA complex with Lac-α-CDE (G3) both in vitro and in vivo.
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Effective treatments for mutated transthyretin (TTR)-related cardiac amyloidosis are limited. Heart transplantation or combined liver-heart transplantation are the most successful options, although results rely on underline mechanism and systemic nature of the disease. In this report, we present the first case of a Caucasian patient with the p. ⋯ Val122Ile mutated TTR-related cardiac amyloidosis have been reported. The patient and some members of his family also had mild peripheral neuropathy suggesting a regional phenotypic heterogeneity of European Caucasian TTR p. Val122Ile.