Could A Single Infusion of Stem Cells Treat Frailty?

As people age, they become more vulnerable to a range of health problems, including frailty, which affects as many as 12 to 24 percent of older adults. 

Frailty is a state of physical decline associated with low-level inflammation, muscle loss, and diminished physical capacity. It makes recovery from minor setbacks like falls harder and increases the risk of dementia and overall mortality. 

A new Phase 2 trial published in Cell Stem Cell found that one infusion of mesenchymal stem/stromal cells (MSCs) may treat frailty, though more studies are needed to confirm the benefits. The company has also tested the same treatment for Alzheimer’s. 

The treatment, called laromestrocel (or Lomecel-B) is made by the biotech company Longeveron. It uses MSCs from the bone marrow harvested from healthy adults and cultivated in a lab.

One infusion to treat frailty?

The trial tested four doses of laromestrocel against a placebo in 148 people with frailty between the ages of 70 to 85. Researchers measured how far participants could walk in six minutes at the start of the trial and again at three, six and nine months. 

“A normal, healthy adult should be able to walk 500 to 600 meters,” study author Dr. Joshua Hare, cardiologist and professor at the University of Miami and who is the co-founder of Longeveron, told Being Patient. “We took people who could only walk 300 meters in six minutes.” 

Over the course of the trial, participants in the placebo group deteriorated while those who received the treatment improved. The gap between the two groups widened over time. 

The treatment group did not walk significantly farther than the placebo group. But there was a dose-response relationship, in which individuals who received a higher dose walked farther than those who received a lower dose or placebo. People who received the highest dose, 200 million cells, walked on average 60 meters farther by the end of the trial. 

Hare believes the treatment may work by improving the health of endothelial cells, which line blood vessels, which was measured as a reduction in the blood protein sTIE2 concurrent with treatment. Further trials are needed to confirm these effects.

The controversy behind MSCs

Not everyone is convinced. Paul S. Knoepfler, professor at UC Davis School of Medicine with expertise in stem cells, who writes The Niche, a blog about the topic, wrote he was skeptical of the results since the effect of the treatment increased for months after one infusion. 

Hare argues this could reflect how MSCs are different from conventional drugs which are short-lived, metabolized and excreted from the body. He believes MSCs may be “a new paradigm in therapeutics” since the effects of the cells “aren’t cleared for months.” 

Others are also skeptical of the MSC angle. Dr. Arnold Kriegstein, a UCSF neurologist and leading expert on stem cells in neurodegenerative disease previously told Being Patient that MSCs “are very unlikely to survive longer than a few days” as “they get filtered by the liver.” 

Hare said that about 1 percent of the MSCs aren’t cleared and may survive for 30 to 40 days in the liver or spleen, and that researchers are still trying to characterize the broad effects of these treatments.

There is also disagreement over whether MSCs are stem cells in the first place. The scientist who discovered mesenchymal stem cells, Arnold Caplan, later disavowed this terminology in 2017, suggesting the name could mislead consumers.

Alongside the randomized trial, Longeveron runs a separate open-label registry trial in the Bahamas, though it deviates from other clinical trials because it requires patients to pay for the experimental treatment out-of-pocket. The registry is not mentioned in the published study. 

UCSF stem cell expert and neurologist Dr. Arnold Kriegstein previously called the arrangement “unethical” and believes it could bias the data collected from these studies.

“It’s reasonable to ask whether the Bahamas registry should have been disclosed in the paper, and whether the editors/reviewers were aware of it,” Knoepfler told Being Patient over email. “In general, I don’t think it’s appropriate to charge patients for access to unproven cell therapies, whether at clinics or via trials.”

Knoepfler said he has concerns about the number of U.S. stem cell therapy companies, like Longeveron, operating just outside U.S. jurisdiction in the Caribbean and Mexico that “offer non-FDA-approved and as yet scientifically unproven” treatments.

What’s next for laromestrocel?

The pathway for approving a frailty treatment is uncertain. Neither US or European regulators consider frailty to be a disease and a larger Phase 3 trial would still be required. Hare sees regulations evolving to accommodate these trials — GLP-1 drugs faced similar regulatory hurdles when researchers were trying to offer them as an obesity treatment. 

Longeveron is also seeking a drug company to partner with them for a larger Alzheimer’s trial, after publishing data from its Phase 2 study last year. 

“I think the regulatory framework will catch up,” said Hare. “Hopefully we’ll be right there and ready.”