Adjunctive Perampanel Oral Suspension in Pediatric Patients From ≥2 to <12 Years of Age With Epilepsy: Pharmacokinetics, Safety, Tolerability, and Efficacy.

Study 232, an open-label pilot study with an extension phase, evaluated the pharmacokinetics and preliminary safety/tolerability and efficacy of adjunctive perampanel oral suspension (≤0.18 mg/kg/d) in epilepsy patients aged ≥2 to <12 years. Patients were grouped into cohorts 1 (aged ≥7 to <12 years) and 2 (aged ≥2 to <7 years). The Core Study included pretreatment (≤2 weeks) and treatment phases (7-week titration; 4-week maintenance; 4-week follow-up [for those not entering the extension]). The extension phase consisted of 41-week maintenance and 4-week follow-up periods. Pharmacokinetic data were pooled with adolescent pharmacokinetic data from phase II/III studies. Population pharmacokinetic analysis showed that perampanel pharmacokinetics was independent of age, weight, or liver function, suggesting age- or weight-based dosing is not required and that the same dose can be given to adults and children to achieve exposures shown to be efficacious. Perampanel was well tolerated and efficacious for ≤52 weeks.

Dual imaging of mRNA and protein production: an investigation of the mechanism of heterogeneity in cationic lipid-mediated transgene expression.

Heterogeneity of transgene expression is a severe disadvantage in the use of cationic lipid-mediated gene vectors. We previously demonstrated that heterogeneity of the post-nuclear delivery process, as well as intracellular trafficking (i.e. nuclear delivery) is a major determinant in the overall heterogeneity in gene expression, when plasmid DNA (pDNA) is transfected to HeLa cells using a lipoplex. In this study, we explored the mechanism underlying this heterogeneity in a post-nuclear transport process by the dual imaging of mRNA and its encoded protein (histone H2B-tagged mTFP1; mTFP1-H2B) in a single cell. To establish a highly sensitive imaging system for mRNA, we used fluorescence in situ hybridization (FISH) combined with tyramide signal amplification (TSA) and a semiconductor quantum dot (QD) probe. The mRNA expression and protein production were quantified by counting the total pixel intensity in the region of interest (r.o.i.) surrounding single cells. As a result, the correlation was poor in a scattered plot of mRNA expression versus protein production in individual cells. These findings demonstrate that cell-to-cell differences in the translation process are also a key factor in heterogeneous gene expression.