Update on clinical trials evaluating the effect of biologic therapy in patients with critical limb ischemia
ABSTRACT Critical limb ischemia (CLI) represents the most severe degree of peripheral arterial disease and is associated with significant morbidity and mortality. In patients with CLI who do not have revascularization options, major amputation is required within 1 year in as many as 40% of patients. Biologic therapies, which include gene therapy and cellular therapy, offer the potential to promote wound healing and prevent amputation in patients who otherwise have poor options for revascularization. Several recent phase 2 trials have shown acceptable safety and suggest that these biological therapies have the potential to improve outcomes in patients with "no-option" CLI. Phase 3 trials are now in progress. This report summarizes the recent results of, and future plans for, gene and cellular therapy clinical trials in patients with CLI.
- SourceAvailable from: Ronnda L. Bartel
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- "All other endpoints were negative . A Phase 3 study is planned to begin in 2012 in 560 CLI patients with rest pain or tissue loss . "
ABSTRACT: There is a large body of preclinical research demonstrating the efficacy of gene and cellular therapy for the potential treatment of severe (limb-threatening) peripheral arterial disease (PAD), including evidence for growth and transcription factors, monocytes, and mesenchymal stem cells. While preclinical research has advanced into early phase clinical trials in patients, few late-phase clinical trials have been conducted. The reasons for the slow progression of these therapies from bench to bedside are as complicated as the fields of gene and cellular therapies. The variety of tissue sources of stem cells (embryonic, adult bone marrow, umbilical cord, placenta, adipose tissue, etc.); autologous versus allogeneic donation; types of cells (hematopoietic, mesenchymal stromal, progenitor, and mixed populations); confusion and stigmatism by the public and patients regarding gene, protein, and stem cell therapy; scaling of manufacturing; and the changing regulatory environment all contribute to the small number of late phase (Phase 3) clinical trials and the lack of Food and Drug Administration (FDA) approvals. This review article provides an overview of the progression of research from gene therapy to the cellular therapy field as it applies to peripheral arterial disease, as well as the position of Aastrom's cellular therapy, ixmyelocel-T, within this field.Stem cell reviews 03/2013; 9(3). DOI:10.1007/s12015-013-9431-x · 3.21 Impact Factor
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ABSTRACT: Life tables were developed to assess the significance of natural enemies on the dynamics of apple ermine moth, Yponomeuta malinellus Zeller, in southwestern Germany and to select parasitoid species for use in the biological control of this pest in Canada. During the study from 1993 to 1995 the abundance of Y. malinellus varied from 1.5 to 4.3 tents per 100 leaf clusters indicating that this was a non-outbreak population. From the life tables it was evident that the impact of egg predators accounted for 25–43% of the total generational mortality of Y. malinellus, more than any other known mortality factor. Percent parasitism varied from 18 to 30%, but the impact of parasitoids in relation to the total generational mortality of Y. malinellus from the life tables was remarkably constant at 11–14%. The loss of potential fecundity had an important influence on the generational mortality of Y. malinellus, but declined from 27% to 15% over the course of this study. This decline corresponded with a rise in the net rate of increase R0 from 1.35 in 1993 to 6.8 in 1995, despite the impact of insect predators and parasitoids on the generational mortality. Yponomeuta malinellus was attacked by five different obligate primary parasitoids, a single obligate hyperparasitoid, and three facultative hyperparasitoids. Of these, the oligophagous egg-larval parasitoid Ageniaspis fuscicollis Dalman (Encyrtidae) and the oligophagous larval-pupal and pupal parasitoid Herpestomus brunnicornis Gravenhorst (Ichneumonidae) were selected as potential biological control agents for Canada due to a minimal degree of interspecific competition.Bulletin of entomological research 03/1998; 88(02):165 - 175. DOI:10.1017/S0007485300025736 · 1.90 Impact Factor