Articles: oligonucleotides.
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Neuromuscul. Disord. · Jan 2014
Randomized Controlled TrialPharmacokinetics and safety of single doses of drisapersen in non-ambulant subjects with Duchenne muscular dystrophy: results of a double-blind randomized clinical trial.
Duchenne muscular dystrophy (DMD) is a progressive, lethal neuromuscular disorder caused by the absence of dystrophin protein due to mutations of the dystrophin gene. Drisapersen is a 2'-O-methyl-phosphorothioate oligonucleotide designed to skip exon 51 in dystrophin pre-mRNA to restore the reading frame of the mRNA. This study assessed safety, tolerability, and pharmacokinetics of drisapersen after a single subcutaneous administration in non-ambulatory subjects. ⋯ Less than proportional increase in exposure was demonstrated over the 3-9mg/kg dose range, though post hoc analysis showed dose proportionality was more feasible over the 3-6mg/kg range. Single doses of drisapersen at 3 and 6mg/kg did not result in significant safety or tolerability concerns; however, at the 9mg/kg dose, pyrexia and transient elevations in inflammatory parameters were seen. The maximum tolerated dose of 6mg/kg drisapersen was identified for further characterization in multiple dose studies in the non-ambulant DMD population.
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Biology of the cell · Jan 2014
Antisense-mediated post-transcriptional silencing of SCN1B gene modulates sodium channel functional expression.
Voltage-dependent sodium channels are membrane proteins essential for cell excitability. They are composed by a pore-forming α-subunit and one or more β subunits. Nine α subunit and five β subunit isoforms have been identified in mammals: β1, its splice variant β1B, β2, β3 and β4. Although they do not form the ion channel pore, β subunits modulate both function as well as expression of sodium channels on cell membrane. ⋯ These results indicate that the β1 subunit may exert an isoform-specific fine-tuned modulation of sodium channel expression.
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J. Am. Coll. Cardiol. · Dec 2013
Randomized Controlled TrialMipomersen, an apolipoprotein B synthesis inhibitor, reduces atherogenic lipoproteins in patients with severe hypercholesterolemia at high cardiovascular risk: a randomized, double-blind, placebo-controlled trial.
This study sought to examine the efficacy and safety of mipomersen for reducing atherogenic lipids and lipoproteins in patients with hypercholesterolemia. ⋯ Mipomersen significantly reduced LDL cholesterol, apolipoprotein B, and lipoprotein(a) in patients with hypercholesterolemia with, or at risk for, coronary heart disease not controlled by existing therapies. (Safety and Efficacy of Mipomersen [ISIS 301012] as Add-On Therapy in High Risk Hypercholesterolemic Patients; NCT00770146).