Now Phase II randomized, placebo-controlled trial findings have verified their initial study, boosting the potential for this stem cell therapy to reverse or forestall the symptoms of frailty. Not only is there no currently approved medical therapy for frailty, the need is expected to grow substantially given the overall aging of the U.S. population.
“It’s a huge need — that’s one of the exciting things,” said Joshua M. Hare, M.D., the Louis Lemberg Professor of Medicine and founding director of ISCI. Frailty is estimated to affect about 10 to 11 percent of seniors, a considerable percentage of the 50 million people older than 65 years experts predict by the year 2050.
Results of the AllogeneiC Human Mesenchymal Stem Cell in Patients with Aging FRailTy via IntravenoUS Delivery (CRATUS) Phase I trial and subsequent CRATUS Phase II trial were simultaneously published online October 12 in The Journals of Gerontology. In an accompanying guest editorial, David G. Le Couter, M.D., Ph.D., professor of medicine at the University of Sydney, and colleagues praised the work.
“These trials represent potential landmarks in the treatment of frailty,” they wrote. “Both studies are early-phase trials of a small number of participants, designed primarily to assess safety, so conclusions about efficacy need to be treated with caution. Even so, the results are striking and, at minimum, pave the way for large randomized Phase III clinical trials.”
“I was very surprised and excited with the results,” Hare said. Replicating their results in the Phase II randomized trials “gives me even greater confidence” in the findings. For example, both trials demonstrated a significant and meaningful increase in six-minute walk tests among older adults with frailty compared to their baseline.
“The idea that we can biologically modify frailty is very exciting,” Hare said. In fact, the research by Hare and his team demonstrate the beneficial effects of mesenchymal stem cell therapy in this population, including their anti-inflammatory effects, pro-regenerative capabilities, and anti-fibrotic actions (meaning they can decrease scar tissue). The investigators have also shown the therapy promotes new vessel growth and improves endothelial function.
“Mesenchymal stem cells are a multifactorial way of offsetting many of the key features of aging,” Hare said.
A unique culture and generous funding make this kind of research at the Institute possible.
“The Interdisciplinary Stem Cell Institute is dedicated to looking for novel therapies for difficult-to-treat problems,” Hare said. “The culture here allows us to do investigator-driven trials, and 2017 has been a great year so far for us, with four stem cell clinical trials — these two on aging and two others addressing cardiovascular disease — including the TRIDENT study evaluating stem cell therapy for ischemic cardiomyopathy.”
The Institute also fosters this kind of study because of generous funding from the Starr Foundation, the Marcus Foundation, the Soffer Family Foundation and the National Institutes of Health, Hare added.
In terms of next steps, the stem cell life sciences company Longeveron acquired the technology and is expanding the findings in a Phase IIb trial at 10 sites nationwide.
“The idea that this came out of the University of Miami and could potentially lead to a new therapy for frailty is groundbreaking,” Hare said.
