Systemic administration of PRO051 in Duchenne's muscular dystrophy.

Background: Local intramuscular administration of the antisense oligonucleotide PRO051 in patients with Duchenne's muscular dystrophy with relevant mutations was previously reported to induce the skipping of exon 51 during pre-messenger RNA splicing of the dystrophin gene and to facilitate new dystrophin expression in muscle-fiber membranes. The present phase 1-2a study aimed to assess the safety, pharmacokinetics, and molecular and clinical effects of systemically administered PRO051.

Methods: We administered weekly abdominal subcutaneous injections of PRO051 for 5 weeks in 12 patients, with each of four possible doses (0.

Chronic UVB exposure enhances in vitro percutaneous penetration of 5-aminulevulinic acid in hairless mouse skin.

Background And Objectives: (Pre)cancerous skin lesions accumulate more protoporphyrin IX (PpIX) upon topical application of 5-aminolevulinic acid (ALA) than the surrounding normal skin. This might be the result of a higher percutaneous penetration of ALA into (pre)cancerous skin.

Study Design/materials And Methods: ALA penetration through (1) healthy skin with intact stratum corneum, (2) healthy skin with reduced stratum corneum (i.

Effect of elevating the skin temperature during topical ALA application on in vitro ALA penetration through mouse skin and in vivo PpIX production in human skin.

An approach to induce increased protoporphyrin IX (PpIX) production in aminolevulinic acid (ALA)-based photodynamic therapy (PDT) of skin lesions is to elevate the skin temperature during topical ALA application. Increased skin temperature may increase the (depth of) penetration of ALA into the skin, which may in turn increase PpIX production (in deeper layers). The effect of skin temperature on in vitro ALA penetration into mouse skin was determined in an in vitro percutaneous penetration model at two different temperatures.

Comparative in vitro percutaneous penetration of 5-aminolevulinic acid and two of its esters through excised hairless mouse skin.

Background And Objectives: ALA esters have been developed to improve PpIX production in ALA-PDT, but they do not perform as well in skin as they do in cells and the bladder.

Study Design/materials And Methods: The in vitro penetration across normal mouse skin of ALA and its methyl and hexyl ester was determined for different application concentrations. ALA and the esters were also applied to tape stripped skin to determine the effect of the stratum corneum.

Systemic component of protoporphyrin IX production in nude mouse skin upon topical application of aminolevulinic acid depends on the application conditions.

Topical application of 5-aminolevulinic acid (ALA) for protoporphyrin IX (PpIX)-based photodynamic therapy of skin cancer is generally considered not to induce systemic side effects because PpIX is supposed to be formed locally. However, earlier studies with topically applied ALA have revealed that in mice PpIX is not only produced in the application area but also in other organs including skin outside the application area, whereas esterified ALA does not. From these results, it was concluded that it is not redistribution of circulating PpIX that causes the fluorescence distant from the ALA application site, but rather, local PpIX production induced by circulating ALA.