Lancet neurology
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Multicenter Study Clinical Trial
Long-term safety and efficacy of patisiran for hereditary transthyretin-mediated amyloidosis with polyneuropathy: 12-month results of an open-label extension study.
Hereditary transthyretin-mediated amyloidosis is a rare, inherited, progressive disease caused by mutations in the transthyretin (TTR) gene. We assessed the safety and efficacy of long-term treatment with patisiran, an RNA interference therapeutic that inhibits TTR production, in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. ⋯ Alnylam Pharmaceuticals.
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Pragmatic Clinical Trial
Safety and efficacy of amantadine, modafinil, and methylphenidate for fatigue in multiple sclerosis: a randomised, placebo-controlled, crossover, double-blind trial.
Methylphenidate, modafinil, and amantadine are commonly prescribed medications for alleviating fatigue in multiple sclerosis; however, the evidence supporting their efficacy is sparse and conflicting. Our goal was to compare the efficacy of these three medications with each other and placebo in patients with multiple sclerosis fatigue. ⋯ Patient-Centered Outcomes Research Institute.
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Review
APOE and Alzheimer's disease: advances in genetics, pathophysiology, and therapeutic approaches.
The APOE ε4 allele remains the strongest genetic risk factor for sporadic Alzheimer's disease and the APOE ε2 allele the strongest genetic protective factor after multiple large scale genome-wide association studies and genome-wide association meta-analyses. However, no therapies directed at APOE are currently available. ⋯ Because all these pathological processes can potentially contribute to cognitive impairment, it is important to use this new knowledge to develop therapies directed at APOE. Several therapeutic approaches have been successful in mouse models expressing human APOE alleles, including increasing or reducing APOE levels, enhancing its lipidation, blocking the interactions between APOE and amyloid-β peptide, and genetically switching APOE4 to APOE3 or APOE2 isoforms, but translation to human clinical trials has proven challenging.