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.
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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; · 5.08 Impact Factor
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ABSTRACT: The primary goals of treatment for critical limb ischemia (CLI) are alleviation of ischemic rest pain, healing of arterial insufficiency ulcers, and improving quality of life. These goals are directed toward preventing limb loss and CLI-related mortality. Arterial revascularization serves as the foundation of a contemporary approach to promote amputation-free survival. Mounting evidence supports a wound-directed angiosome revascularization approach, increasingly achieved with endovascular techniques. Innovations in technology and wound-perfusion strategy have advanced patient care and are accelerating the pace of CLI treatment. The evolving angiosome revascularization approach has been augmented with a multidisciplinary wound care strategy that deserves particular emphasis. These state-of-the-art advances in CLI management are reported herein with considerations for the future treatment of CLI.Current Cardiology Reports 06/2013; 15(6):363.