Ray Chen

© AlphaMed Press.Somatic cells can be reprogrammed to an altered lineage by overexpressing specific transcription factors. To avoid introducing exogenous genetic material into the genome of host cells, cell-penetrating peptides can be used to deliver transcription factors into cells for reprogramming. Position-dependent C-end rule cell- and tissue-penetrating peptides provide an alternative to the conventional cell-penetrating peptides, such as polyarginine. In this study, we used a prototypic, already active CendR peptide, RPARPAR, to deliver the transcription factor SOX2 to retinal pigmented epithelial cells. We demonstrated that RPE cells can be directly reprogrammed to a neuronal fate by introduction of SOX2. Resulting neuronal cells expressed neuronal marker mRNAs and proteins and downregulated expression of RPE markers. Cells produced extensive neurites and developed synaptic machinery capable of dye uptake after depolarization with potassium. The RPARPAR-mediated delivery of SOX2 alone was sufficient to allow cell lineage reprogramming of both fetal and stem cell-derived RPE cells to become functional neurons.

© 2015, American College of Rheumatology. Objective More than 1 in 4 Medicare beneficiaries with rheumatoid arthritis use high-cost biologic disease-modifying antirheumatic drugs, and spending for these drugs has risen sharply for Medicare Part D. Our aim was to conduct the first systematic, national investigation of how Part D plans cover biologic DMARDs and to determine patients' financial burden under current cost-sharing structures. Methods We performed a cross-sectional analysis of Part D plan formularies in 50 states and Washington, DC using the January 2013 Centers for Medicare and Medicaid Services Prescription Drug Plan Formulary and Pharmacy Network Files. We calculated the percentage of plans covering each DMARD as well as the percentage requiring prior authorization and/or coinsurance. We also compared biologic drug coverage in Medicare Advantage prescription drug plans to that in Medicare Part D stand-alone plans. Results All plans covered at least 1 biologic DMARD, but the vast majority required prior authorizations. Nearly all plans required patients to pay a coinsurance percentage rather than a fixed dollar copayment. This translated into mean out-of-pocket costs of $2,712-$2,774 before reaching the catastrophic phase of coverage, during which beneficiaries pay 5% of drug costs. Medicare Advantage prescription drug plans covered more individual biologic DMARDs than did Medicare Part D stand-alone plans, but Medicare Advantage prescription drug plans required higher average coinsurance. In contrast, 6 of 9 nonbiologic DMARDs were covered by nearly all plans without prior authorizations at fixed copayments averaging $5-$10/month. Conclusion Nationally, nearly all Part D plans cover at least 1 biologic DMARD, but the vast majority require cost sharing sufficiently high to risk significant financial burden to patients.