Longeveron Inc., a clinical stage biotechnology company developing regenerative cell therapy for life-threatening rare pediatric and chronic aging-related conditions, announced that results of its Phase 2b clinical trial were published today in Cell Stem Cell, a Cell Press Journal.

The Phase 2b results demonstrated that intravenous laromestrocel, a mesenchymal stem cell product, improved the physical condition of patients with age-related clinical frailty after nine months, compared to placebo. The full publication is available on the Cell Stem Cell website here.

A single dose of stem cells can help older people with frailty to build up their endurance, a study finds. The study’s authors say that the results offer the strongest evidence to date for an effective treatment for frailty, which affects as many as one-quarter of people aged 50 or older.

“For the first time, you have a treatment that targets accelerated ageing,” which can manifest as frailty, says Jorge Ruiz, a study author and geriatrician at Memorial Healthcare System in Hollywood, Florida.

Debilitating condition

There is no single accepted definition of frailty. But researchers generally agree that people with the condition have lower physical endurance and a higher risk of dying compared with others of the same age. They also take longer to recover from events such as a fall.

Because frailty describes a set of physical symptoms that do not share a single molecular cause, relatively few research groups have tried to develop treatments specific to the condition.

Joshua Hare, chief science officer of Longeveron in Miami, Florida, which is developing the therapy, and his colleagues decided to address frailty using mesenchymal stem cells, which are found in tissues such as bone marrow and fat. The cells can differentiate into a wide variety of tissue types, including bone, cartilage and muscle, and release anti-inflammatory signalling molecules.

Adding to their promise, the cells have few of the surface proteins that would usually trigger a reaction by a recipient’s immune system. This means that people infused with these cells don’t need to take immunosuppressive medications that could lead to fatal infections in people who are already frail.

Power walk

The authors collected stem cells from donated bone marrow and grew them in the laboratory. They administered one of four doses of stem cells to 118 participants and a placebo to 30. All participants were between 70 and 85 years old and had frailty, although all could walk.

Nine months after treatment, those who had received the highest dose of stem cells walked about 60 metres farther, on average, in a six-minute walk test than they had before receiving the therapy — about a 20% improvement.

Participants who received stem cells were also more likely than those who did not to improve on a clinical scale of frailty. “It is non-trivial to improve a whole grade of frailty,” says Kenneth Rockwood, a geriatrician at Dalhousie University in Halifax, Canada, who created that measurement. The improvements in the walk test and frailty score “are most encouraging”.

Researchers say that the effects of accelerated ageing are multifactorial and hard to reverse, so it was exciting that this study found a benefit, rather than just a halt to a progressive decline. Had the authors followed up the participants for longer, they might have seen an even more impressive result, says Alice Kane, who researches ageing at the Institute for Systems Biology in Seattle, Washington.

Unknown mechanism

How the therapy works is unclear, because mesenchymal stem cells have such wide-ranging effects.

The researchers propose that the treatment reduced inflammation in the tissue that surrounds small blood vessels, because people who received the stem cells had lower levels of an inflammatory biomarker specific for that tissue type than did control participants.

The authors say they did not detect any serious side effects. “Nobody got a fever, nobody got a rash, nobody had anything serious,” says Hare. Each of those side effects has been observed in recipients of other stem-cell therapies.

Despite its promise, the therapy does not have a clear-cut path to the clinic, researchers say, because the US and European regulatory authorities do not consider frailty to be a disease. Hare says that approval of the treatment might be possible if his company can show that it reduces the risk of falls or improves survival after surgery.