Hepatocyte Growth Factor to Improve Walking Performance in PAD: the HI-PAD Study

As a co-investigator in the HI-PAD study (Northwestern University, PI: Mary McGrae McDermott, MD), I will measure changes in calf skeletal muscle MyoD, Pax7, and capillary density in response to hepatocyte growth factor vs. placebo in frozen human muscle biopsies shipped to the University of Kentucky from Northwestern University. We will also perform immunohistochemical analysis of autophagy measures. We have budgeted for immunohistochemical analyses of muscle cross-sections for approximately 22 specimens in year one and 21 specimens in year two. This is based on the fact that we anticipate that approximately 2/3 of the 33 participants randomized during the two-year study will undergo muscle biopsy and that approximately 90% of those who undergo a baseline muscle biopsy will have a follow-up muscle biopsy. Digital microscopic images, as well as quantification of the images, will be provided to investigators at Northwestern. We will communicate regularly by phone, email and video conferencing, and I will attend at least one meeting annually at Northwestern University. This component of the HI-PAD trial enables us to delineate biologic pathways underlying the beneficial effects of hepatocyte growth factor in patients with PAD. Identifying biologic mechanisms will help identify new therapies, with similar biologic actions, that improve walking performance in people with peripheral artery disease.