Peripheral Vascular Disease
Peripheral vascular disease (PVD), which is sometimes referred to as peripheral arterial disease (PAD), is characterized by chronic poor blood flow in the lower extremities, which can cause pain, ischemic lesions or ulcers, and sepsis. Over time this condition can progress to critical limb ischemia, and eventually lead to limb amputation. According to the 2010 American Heart Association annual statistical report on heart disease, approximately 8 million Americans have PVD, and suffer significant morbidity and mortality as a result. In 2004, the direct and indirect costs of treating PVD were estimated to be over $2 billion dollars annually in the United States alone.
Current treatment of PVD depends on the severity of the disease. Current approaches include treatment to reduce risk factors, drug therapy to reduce clotting and plaque formation, or surgical intervention in an attempt to revascularize the region of ischemic damage. However, many of the approved pharmaceutical interventions have significant side effects, and many patients are unfit candidates for revascularization due to advanced age, advanced ischemia or the presence of other complicating conditions. Additionally, revascularization is only successful 44% of the time.
Recent studies suggest that an increase in the collateral vascular network may offer protection from ischemic episodes. Collaterals normally form, remodel and enlarge around the site of blockage allowing blood flow to bypass the occluded artery and allow perfusion of the ischemic tissue. However, naturally occurring collateral development is adversely affect by age, hypercholesterolemia, diabetes and smoking and is insufficient to support adequate blood flow to the affected tissues in many PVD patients, especially during exertion.
Given that the vascular growth process requires coordination of a complex array of molecular mechanisms, we believe that the targeted delivery of multiple protein factors that can promote angiogenesis and protect and repair ischemic tissue could be an effective approach to enhance healing of ischemic tissue. The dynamic and responsive nature of MultiStem and the ability to express multiple factors that can influence the healing and tissue repair process makes it an attractive cellular therapy addition to current therapies. MultiStem has been shown to secrete angiogenic factors, and currently, two clinical programs for ischemic injuries (stroke and acute myocardial infarction) are in development. In animal models of PVD, MultiStem treatment has resulted in significant improvement in blood flow, vessel density, muscle function and stimulated muscle regeneration. Even in models of severe limb ischemia, as evidence by increased tissue necrosis, treatment with these cells expanded the collateral bed by 21 days and showed improvement in muscle function and a decrease in toe necrosis and limb loss compared to vehicle treated controls. We intend to leverage this preclinical data and related preclinical and clinical data from other programs to move into clinical development as resources and opportunities permit, or as part of a business partnership.
Figure: Administration of human MAPCs in a rodent model of peripheral vascular ischemia results in significantly improved blood flow in the hind limb region by day 30 relative to control animals treated with PBS. Images from Aaranguren et al Cell Transplant. 2011;20(2):259-69.