Ischemia-repairing cells fall short for treating intermittent claudication
NEW ORLEANS – Therapy with cells known to repair ischemic damage does not improve intermittent claudication of the legs in unselected patients, according to data from the randomized, phase II PACE trial reported at the American Heart Association scientific sessions. But some patients had evidence of new vessel formation.
“Administration of ALDH [aldehyde dehydrogenase] bright cells was feasible and safe, [but] administration at this dose and in this PAD [peripheral artery disease] cohort did not change peak walking time or MRI-based anatomic and perfusion endpoints,” reported Emerson C. Perin, MD, director of Clinical Research for Cardiovascular Medicine and medical director of the Stem Cell Center, both at the Texas Heart Institute, Houston.
However, “the MRI techniques developed and applied for the first time in a multicenter PAD clinical trial are now available for application in future PAD clinical research to determine if a clinically relevant therapeutic benefit might be achieved from cells or any other promising intervention,” he noted.
“One of the things in peripheral vascular disease that’s always been true is that peak walking time is a good clinical endpoint,” said session panelist Doris A. Taylor, PhD, director of Regenerative Medicine Research at the Texas Heart Institute. “[You] proposed some MRI parameters, but those didn’t correlate with peak walking time. So is the takeaway from this trial these MRI parameters? And if they don’t necessarily correlate, why would you advocate for them?”
Dr. Perin replied: “PAD is kind of the stepchild of cardiovascular medicine, it’s very poorly understood. And I think with the PACE trial, we’ve actually taken a huge step in understanding how we can treat these patients and how to study these patients.”
“Even though intermittent claudication or PAD starts with the flow limitation, what you wind up getting later down the road is not something that just relates to flow,” he elaborated. “We were able to study flow completely in this study – we owned it. What we weren’t able to study, and at the time we couldn’t, but now we can, is the metabolic, endothelial, and mitochondrial function. That is, what’s happening at the level of the muscle that is the missing link, together with the flow, that will give us these answers. So I think PACE [Patients With Intermittent Claudication Injected With ALDH Bright Cells] was very important to give us a greater understanding of where we can go now in PAD research.”
Trial details
Between 1 and 3 million people in the United States live with claudication, Dr. Perin noted when introducing the study. “It’s a very significant problem and a problem for which we really don’t have good solutions. We have one medicine [cilostazol], revascularization surgery, and stents that have recurrence – things that are less than perfect. There are also exercise programs, which not everyone has access to.”
