Peripheral arterial disease: New pharmaceutical therapies to treat intermittent claudication symptoms, prevent ischemic events and to induce angiogenesis
This report focuses on new oral therapies to treat peripheral arterial disease (PAD). Pharmaceuticals to treat the spectrum of disease severity include those for the symptoms of intermittent claudication (IC), medications to prevent ischemic events, as well as agents to induce angiogenesis and cell therapies to treat IC and critical limb ischemia (CLI).
Primarily formatted as a series of tables, the analysis is limited to medications currently in human clinical trials as of December 31, 2007. Organized by type of therapy, each table includes information on the company or sponsor, the drug, mode of action, development status, clinical trial comments and where applicable the projected date of market entry.
Oral pharmaceuticals to treat the symptoms of IC include stand-alone therapies and those to be employed in conjunction with supervised exercise therapy. Since a large number of new IC therapies have failed to demonstrate efficacy in late stage clinical trials, a discussion of these is included.
New anticoagulants and antiplatelets are assessed by primary mode of action with the anticoagulants further categorized as thrombin inhibitors, factor Xa inhibitors and new heparin formulations. More than ten antiplatelet agents with various modes of activity are under investigation for prevention of ischemic events in PAD patients.
In the 1990s several small trials employing one or two proteins in multigene growth factor families demonstrated the safety of therapeutic angiogenesis in peripheral ischemia. However, efficacy was mixed.
Current gene and protein research is focused on plasmid therapies and genetically engineered factors to stimulate angiogenesis. Research employing cell therapies, particularly autologous stem cells harvested from bone marrow or peripheral blood mononuclear cells has become very active, with over 20 trials ongoing worlwide.
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