A single dose of stem cells can significantly enhance physical endurance in older adults experiencing frailty. According to 1 in 10 people over the age of 65 are affected by this condition, as highlighted by a recent study published in the journal Cell Stem Cells.

The randomized, placebo-controlled trial investigated four escalating doses of laromestrocel, a treatment derived from donated bone marrow, in 148 adults aged 70 to 85 who were diagnosed with frailty.

After nine months, participants receiving the highest dose walked an average of 60 meters further than those given a placebo during a standard six-minute walk test, reflecting a remarkable 20% improvement.

“The results were astonishing,” said Dr. Joshua Hare, chief scientific officer of Ronnebellon, the company behind the treatment. He emphasized, “We noted a clear correlation based on dosage over time; higher doses led to a more pronounced increase in the six-minute walk test.”

Frailty is a prevalent but often misunderstood medical condition characterized by heightened vulnerability to stressors such as infections, falls, and surgical procedures, significantly beyond what is typically expected from normal aging.

This condition includes decreased muscle strength and endurance, leading to a sharply increased risk of disability, hospitalization, and mortality. According to the British Geriatrics Society, individuals with severe frailty are five times more likely to die within a year compared to those without frailty.

“When you observe 80-year-olds, some require 24-hour care in nursing homes, while others lead vibrant lives, participating in activities like tennis and golf,” Hare noted. “The biological differences play a crucial role.”

Hare suggests that inflammation, often exacerbated by age-related factors, is a significant contributor. As individuals age, their immune systems become dysregulated, with higher levels of inflammatory signaling molecules known as cytokines.

This chronic inflammation can damage blood vessels, deplete stem cell reserves, and accelerate muscle loss, culminating in a condition known as sarcopenia.

The result is frailty; the body becomes less capable of self-repair and responding to physical or medical stressors.

Current treatments primarily focus on nutritional support and physical therapy.

“Typical interventions are rather straightforward,” Hare explained. “We recognized the need to address this at a biological level, as we understand the underlying issues.”

Mesenchymal stem cells, naturally found in bone marrow and other tissues, are of great scientific interest due to their immune-modulating capabilities.

Importantly, these cells possess minimal surface proteins responsible for immune rejection, minimizing the need for immunosuppressive drugs—an important consideration for vulnerable patients.

Hare and his team harvested stem cells from donated bone marrow and administered them intravenously to participants, who were either given a placebo or one of four doses of lalometrocel in a double-blind setup.

The results, monitored every three months over nine months, clearly indicated that increased stem cell doses significantly enhanced walking distance. Conversely, the placebo group exhibited expected declines in physical performance typical of frail individuals aged 75 and older.

Patient-reported outcomes from questionnaires assessing physical performance, upper body strength, and mobility confirmed improvements that aligned with objective measurements from the walk tests. Participants also showed progress on a doctor-rated frailty scale ranging from 1 (most frail) to 9 (least frail).

“One-third of treated participants achieved health scores of 2 or 3,” Hare stated, indicating they were no longer deemed frail.

Researchers identified soluble Tie2 as a potential biological marker for therapeutic efficacy, a protein released into the bloodstream upon inflammation or breakdown of blood vessel walls. Patients receiving stem cells showed decreasing levels of this marker in a dose-dependent manner.

“This evidence suggests that medical interventions can potentially reverse frailty,” stated Dr. Andrew Steele, Director of the Longevity Initiative. He highlighted the challenge of achieving physical activity in frail individuals and celebrated the remarkable potential of stem cell infusions to not only slow decline but also to foster tangible improvement.

Nonetheless, the study raises key questions. The wide-ranging effects of stem cells leave uncertainties about the exact mechanisms at play.

“These cells might be targeting areas where they are most needed and regenerating cells,” said Steele. “Alternatively, they could be releasing a mix of anti-aging molecules that rejuvenate the body’s own cells.”

The follow-up period lasted nine months, leaving questions regarding the sustainability of improvements and the effectiveness of repeated doses.

Hare’s team has conducted long-term trials with multiple doses, showing preliminary evidence that participants improve without side effects and maintain benefits, though the evidence lacks robustness compared to controlled trials. Formal studies on repeat dosing are on the horizon.

Furthermore, significant regulatory challenges loom. Currently, frailty is not recognized as a disease by the U.S. Food and Drug Administration or the European Food and Drug Administration, complicating the approval process.

“It will be a tough fight,” Hare cautioned, adding that the approval pathway for laromestrocel could be expedited for Alzheimer’s disease, with promising results in related clinical trials evidenced in another study.

“We believe treatments for age-related frailty will likely be approved alongside those for Alzheimer’s, given that the latter is a well-defined condition with pressing unmet needs.”

To date, the trials indicate promise, presenting strong evidence that frailty is not an inevitable consequence of aging but a biological process that can be at least partially reversed.

“Human lifespan has nearly doubled in the last 120 years,” Hare remarked. “However, healthy life expectancy hasn’t progressed at the same pace. There will always be an end-of-life phase marked by disability and frailty.”

If progress continues, the gap between lifespan and healthy living could finally begin to close.

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