Slow walking speed is a common feature of frailty
Gordon Scammell/Loop Images/Universal Images/Getty Images
An experimental stem cell therapy could treat frailty by targeting the condition at its biological roots. Frailty – which increases the risk of falls and infections – is usually only reduced through lifestyle changes, such as strength and balance training. But now it appears that a new infusion of stem cells from young, healthy people into older individuals significantly improved their mobility.
“Frailty is a major source of disability and reduced quality of life in older individuals,” says Joshua Hare of Longeveron, a biotechnology company in Miami, Florida. “There is a huge unmet need to find biological treatments.”
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 impairment of metabolic processes that cause muscles to contract. The treatment – called laromestrocel – consists of mesenchymal stem cells that can develop into many different types of cells, including muscle and cartilage, taken from healthy bone marrow donors aged 18 to 45.
After success in early studies for frailty – which affects around 1 in 4 people aged 65 and over – they have now tested different doses of laromestrocel against placebo in a larger group of 148 people.
The researchers measured how far the participants – who were aged 74 to 76 and had mild to moderate frailty – could walk in 6 minutes before and after laromestrocel. They found that a single infusion improved their performance 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 – and rose to 63 meters after nine months.
Laromestrocel inhibits enzymes called matrix metalloproteinases, according to the team, which have a degenerative effect on structural proteins in blood vessels and other tissues. This means that laromestrocel can regenerate the vascular system, which then benefits muscle fibers involved in endurance, says Hare.
However, it did not lead to improvements in walking speed or grip strength. “Clinically, the most important issue is the 6-minute walk distance, which is known to correlate with health status and longevity,” says Hare.
“This seems very promising,” says Daisy Wilson of the University of Birmingham in the UK. “I was impressed by the overall change demonstrated within the 6-minute walk.”
Also, the trial may have led to a biomarker of frailty, which could help identify people who would benefit most from treatment – possibly even before symptoms appear. The researchers screened a panel of eight potential biomarkers known to be involved in inflammation and blood vessel formation. When they analyzed the participants’ blood, they observed that the levels of a fragment called sTIE2, which reflects impaired vascular function, gradually decreased with increasing doses of laromestrocel.
This suggests that people with high sTIE2 may benefit most from the therapy, says Wilson. “Frailty is very heterogeneous,” she says. “I think the most important part of geroprotector medicine (interventions that slow the aging process) going forward is 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 this is likely to be, I’m not sure how you would be able to justify its use when there have been trials with gait programs, which have improved the 6-minute walk test (performance) by more than 50 meters,” she says. “My second thought is how difficult it is to get stem cells from volunteers. There have to be a lot of volunteers to treat everyone with frailty.”
Hare counters this by saying that various companies are making technological advances to scale up stem cell therapies to reach more people. “There is a lot of work going on regarding the ability to make such stem cells in large quantities, and I’m sure the need will be met,” he says.
Topics:
