Ocular Gene Therapy in a Patient with Dystrophic Epidermolysis Bullosa.

Dystrophic epidermolysis bullosa is a rare genetic disease caused by damaging variants in , which encodes type VII collagen. Blistering and scarring of the ocular surface develop, potentially leading to blindness. Beremagene geperpavec (B-VEC) is a replication-deficient herpes simplex virus type 1-based gene therapy engineered to deliver functional human type VII collagen.

Trial of Beremagene Geperpavec (B-VEC) for Dystrophic Epidermolysis Bullosa.

Background: Dystrophic epidermolysis bullosa is a rare genetic blistering skin disease caused by mutations in , which encodes type VII collagen (C7). Beremagene geperpavec (B-VEC) is a topical investigational herpes simplex virus type 1 (HSV-1)-based gene therapy designed to restore C7 protein by delivering .

Methods: We conducted a phase 3, double-blind, intrapatient randomized, placebo-controlled trial involving patients 6 months of age or older with genetically confirmed dystrophic epidermolysis bullosa.

In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial.

Recessive dystrophic epidermolysis bullosa (RDEB) is a lifelong genodermatosis associated with blistering, wounding, and scarring caused by mutations in COL7A1, the gene encoding the anchoring fibril component, collagen VII (C7). Here, we evaluated beremagene geperpavec (B-VEC), an engineered, non-replicating COL7A1 containing herpes simplex virus type 1 (HSV-1) vector, to treat RDEB skin. B-VEC restored C7 expression in RDEB keratinocytes, fibroblasts, RDEB mice and human RDEB xenografts.

Preclinical Evaluation of a Modified Herpes Simplex Virus Type 1 Vector Encoding Human TGM1 for the Treatment of Autosomal Recessive Congenital Ichthyosis.

Autosomal recessive congenital ichthyosis (ARCI) is a diverse group of cornification diseases associated with severe clinical complications and decreased quality of life. Germline mutations in the TGM1 gene, which encodes the enzyme TGM1, are the predominant cause of ARCI. These TGM1 mutations trigger the abnormal epidermal differentiation and impaired cutaneous barrier function observed in patients with ARCI.

Thrombospondin-1 Is a Major Activator of TGF-β Signaling in Recessive Dystrophic Epidermolysis Bullosa Fibroblasts.

Mutations in the gene encoding collagen VII cause the devastating blistering disease recessive dystrophic epidermolysis bullosa (RDEB). RDEB is characterized by severe skin fragility and nonhealing wounds aggravated by scarring and fibrosis. We previously showed that TSP1 is increased in RDEB fibroblasts.

Pharmacokinetics of lisdexamfetamine dimesylate and its active metabolite, d-amphetamine, with increasing oral doses of lisdexamfetamine dimesylate in children with attention-deficit/hyperactivity disorder: a single-dose, randomized, open-label, crossover study.

Background: Lisdexamfetamine dimesylate (LDX) is a long-acting oral prodrug stimulant indicated for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children 6 to 12 years old and in adults. Information on the pharmacokinetic profile of LDX in children with ADHD is lacking.

Objective: The aim of this study was to assess the pharmacokinetic properties of d-amphetamine delivery from LDX, and intact LDX with increasing doses of LDX administered in children with ADHD.

Double-blind, placebo-controlled study of the efficacy and safety of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder.

Objective: To evaluate the efficacy and safety of 30, 50, and 70 mg/day lisdexamfetamine dimesylate compared with placebo in adults with attention-deficit/hyperactivity disorder (ADHD).

Method: Following a 7- to 28-day washout, 420 adults aged 18 to 55 years with moderate to severe ADHD (DSM-IV-TR criteria) were treated with 30, 50, or 70 mg/day lisdexamfetamine or placebo, respectively, for 4 weeks (N = 119, 117, 122, and 62, respectively). The 50- and 70- mg/day groups underwent forced-dose titration.

Metabolism, distribution and elimination of lisdexamfetamine dimesylate: open-label, single-centre, phase I study in healthy adult volunteers.

Background And Objectives: Attention-deficit/hyperactivity disorder (ADHD) in children often persists into adulthood and is potentially associated with significant social and occupational impairments. It is important to understand the effects of pharmacological treatments of ADHD in adults. This study aimed to assess the absorption, metabolism and elimination of lisdexamfetamine dimesylate in normal, healthy adult subjects following a single oral dose.

Long-term effectiveness and safety of lisdexamfetamine dimesylate in school-aged children with attention-deficit/hyperactivity disorder.

Introduction: Lisdexamfetamine dimesylate (LDX), a prodrug stimulant, is indicated for attention-deficit/hyperactivity disorder (ADHD) in children 6-12 years of age and in adults. In short-term studies, once-daily LDX provided efficacy throughout the day. This study presented here was conducted to assess the long-term safety, tolerability, and effectiveness of LDX in 6- to 12-year-olds with ADHD.

Relative bioavailability of lisdexamfetamine 70-mg capsules in fasted and fed healthy adult volunteers and in solution: a single-dose, crossover pharmacokinetic study.

The relative bioavailability of oral lisdexamfetamine dimesylate, a prodrug of d-amphetamine, and active d-amphetamine was assessed in an open-label, single-dose, 3-treatment, 3-period, randomized, crossover study in 18 healthy adult volunteers. Following a fast of at least 10 hours, subjects were administered an intact capsule of 70 mg lisdexamfetamine, a solution containing the capsule contents, or an intact capsule with a high-fat meal. Standard meals started 4 hours following lisdexamfetamine administration.

Multiple daily-dose pharmacokinetics of lisdexamfetamine dimesylate in healthy adult volunteers.

Objective: To evaluate the pharmacokinetics of lisdexamfetamine dimesylate (LDX; Vyvanse) in fasting healthy adult volunteers.

Background: LDX is the first pro-drug stimulant and is indicated for the treatment of attention-deficit/hyperactivity disorder. LDX was developed with the goal of providing an extended effect that is consistent throughout the day, with a reduced potential for abuse, overdose toxicity, and drug tampering.

Toxicity profile of lisdexamfetamine dimesylate in three independent rat toxicology studies.

Lisdexamfetamine dimesylate (LDX) is a d-amphetamine prodrug developed for the treatment of attention-deficit/hyperactivity disorder. The toxicity profile of orally administered LDX has been evaluated in rats. In an acute study, LDX doses of 60 mg/kg and higher caused increased motor activity.

Lisdexamfetamine dimesylate and mixed amphetamine salts extended-release in children with ADHD: a double-blind, placebo-controlled, crossover analog classroom study.

Background: Lisdexamfetamine dimesylate is a therapeutically inactive prodrug in which d-amphetamine is covalently bound to l-lysine, a naturally occurring amino acid. Pharmacologically active d-amphetamine is released from lisdexamfetamine following oral ingestion.

Methods: This phase 2, randomized, double-blind, placebo- and active-controlled crossover study compared the efficacy and safety of lisdexamfetamine (LDX: 30, 50, or 70 mg) with placebo, with mixed amphetamine salts extended-release (MAS XR: 10, 20, or 30 mg) included as a reference arm of the study, in 52 children aged 6 to 12 years with attention-deficit/hyperactivity disorder (ADHD) in an analog classroom setting.

Efficacy and tolerability of lisdexamfetamine dimesylate (NRP-104) in children with attention-deficit/hyperactivity disorder: a phase III, multicenter, randomized, double-blind, forced-dose, parallel-group study.

Background: Lisdexamfetamme dimesylate (LDX) is a therapeutically inactive amphetamine prodrug. It was developed with the goal of providing an extended duration of effect that is consistent throughout the day, with a reduced potential for abuse, overdose toxicity, and drug tampering. Following ingestion, the pharmacologically active d-amphetamine molecule is gradually released by rate-limited hydrolysis.

An evaluation of the cytochrome p450 inhibition potential of lisdexamfetamine in human liver microsomes.

The human cytochrome P450 (P450) system is implicated in many drug interactions. Lisdexamfetamine dimesylate (NRP104), the proposed generic name for a new agent under investigation for treatment of attention deficit hyperactivity disorder, was recently analyzed for inhibitory drug-drug interactions with seven major P450 isoforms using pooled human liver microsomes. Probe substrates were used near the K(m) concentration values reported in the literature for CYP1A2 (phenacetin), CYP2A6 (coumarin), CYP2B6 (bupropion), CYP2C9 (tolbutamide), CYP2C19 ([S]-mephenytoin), CYP2D6 (dextromethorphan), and CYP3A4 (midazolam and testosterone), and lisdexamfetamine was evaluated at concentrations ranging from 0.