Frailty can be alleviated by infusion of stem cells from young people

Experimental stem cell therapy could treat frailty by targeting its biological roots. Frailty – which increases the risk of falls and infections – is usually only alleviated with lifestyle changes such as strength training and balance exercises. But now it appears that a new infusion of stem cells from young, healthy people into older individuals has greatly improved their mobility.

“Frailty is a major source of disability and reduced quality of life for older individuals,” he says Joshua Hare at Longeveron, a biotech company in Miami, Florida. “There is a great unmet need to find a biological treatment.”

Hare and his colleagues at Longeveron are developing a therapy that they hope will target some of the underlying mechanisms of aging, such as inflammation and disruption of the metabolic processes that cause muscle contraction. The therapy – called laromestrocel – consists of mesenchymal stem cells, which can develop into many different cell types, including muscle and cartilage, taken from healthy bone marrow donors between the ages of 18 and 45.

After the success of initial stage of trials for frailty – which affects around 1 in 4 people aged 65 and over – have now tested different doses of laromestrocel against a placebo in a larger group of 148 people.

The researchers measured how far the participants—who were between the ages of 74 and 76 and had mild to moderate frailty—were able to walk in 6 minutes before and after laromestrocel. They found that a single infusion improved their efficacy in a dose-dependent manner, without serious safety concerns. For example, those who received the maximum dose could walk 41 meters further than those who received a placebo six months after the infusions – increasing to 63 meters after nine months.

Laromestrocel inhibits enzymes called matrix metalloproteinases, which have a degenerative effect on structural proteins in blood vessels and other tissues, according to the team. This means that laromestrocel could regenerate the vascular system, which then benefits the muscle fibers involved in endurance, Hare says.

However, it did not improve walking speed or grip strength. “Clinically, the most important issue is the 6-minute walk, which is known to correlate with health and longevity,” says Hare.

“This looks very promising,” he says Daisy Wilson at the University of Birmingham in Great Britain. “I was amazed at the total change demonstrated within 6 minutes of walking.

What’s more, the study could lead to a biomarker of frailty that could help identify people who will benefit most from treatment — perhaps even before symptoms appear. The researchers examined a panel of eight potential biomarkers known to be involved in inflammation and blood vessel formation. Analyzing the participants’ blood, they observed that levels of a fragment called sTIE2, which reflects impaired vascular function, progressively decreased with increasing doses of laromestrocel.

This suggests that people with high sTIE2 could benefit the most from the therapy, Wilson says. “Frailty is very heterogeneous,” he says. “I think the most important part of geroprotector medicine. [interventions that slow the ageing process] moving forward means matching the right patient to the right treatment.”

However, she also raised practical concerns about the cost of stem cell therapies and their feasibility. “Given how expensive it’s likely to be, I’m not sure how you would be able to justify using it when there have been trials of walking programs that improved the 6-minute walk test. [performance] by more than 50 meters,” he says. “My other thought is how difficult it is to get stem cells from volunteers. It would take a lot of volunteers who would be gentle with everyone.”

Hare counters that various companies are making technological advances to expand stem cell therapies to reach more people. “There’s a lot of work going on to be able to produce these kinds of stem cells in large quantities, and I’m confident that that need will be met,” he says.

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