Remco L A de Vrueh

Learn More
More than 25 years of orphan drug regulations have yielded several new treatments for patients with rare diseases. Here, we show that successful translation of rare disease research into an orphan drug discovery and development programme is dependent on the disease class, its prevalence and the disease-specific scientific output. Our findings indicate that(More)
Lipoproteins are endogenous particles that transport lipids through the blood to various cell types, where they are recognised and taken up via specific receptors. These particles are, therefore, excellent candidates for the targeted delivery of drugs to various tissues. For example, the remnant receptor and the asialoglycoprotein receptor (ASGPr), which(More)
BACKGROUND Drugs for rare diseases, so-called orphan drugs, are often intended for serious or chronically debilitating diseases. Safety information is more limited at the time of approval for orphan drugs as a result of various factors, such as the limited number of patients in clinical trials, quality of the clinical trials and special approval procedures.(More)
Systemically administered phosphorothioate antisense oligodeoxynucleotides can specifically affect the expression of their target genes, which affords an exciting new strategy for therapeutic intervention. Earlier studies point to a major role of the liver in the disposition of these oligonucleotides. The aim of the present study was to identify the cell(More)
It has been reported that conjugating acyclovir, a potent antiviral with low oral bioavailability, to L-valine increases its urinary excretion in rats. However, it was also reported that this increase is not found for the D-valine ester, suggesting that a carrier-mediated mechanism is involved in its intestinal absorption. Therefore, mechanisms involved in(More)
Several studies have shown improved efficacy of cholesteryl-conjugated phosphorothioate antisense oligodeoxynucleotides. To gain insight into the mechanisms of the improved efficacy in vivo, we investigated the disposition of ISIS-9388, the 3'-cholesterol analog of the ICAM-1-specific phosphorothioate oligodeoxynucleotide ISIS-3082, in rats. Intravenously(More)
BACKGROUND We determined whether the market exclusivity incentive of the European Orphan Drug Regulation results in a market monopoly or that absence of another Orphan Medicinal Product (OMP) for the same rare disorder, a so-called follow-on OMP, is a matter of time or market size. In the interest of rare disorder patients better understanding of the effect(More)
BACKGROUND We studied to what extent the level of scientific knowledge on exceptionally rare metabolic inherited diseases and their potential orphan medicinal products is associated with sponsors deciding to apply for an orphan designation at the US Food and Drug Administration (FDA) or the European Medicines Agency (EMA). METHODS All metabolic diseases(More)
AIM A clinical trial is only as reliable as its outcomes, therefore the careful and systematic selection of outcome measures is extremely important. Currently, the selection of outcome measures for clinical trials designed to evaluate new drugs in patients with mitochondrial disorders is inefficient and has not been addressed systematically. Given that(More)