Frailty can be eased with an infusion of stem cells from young people
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 disease at its biological roots. Frailty – which increases the risk of falls and infections – is usually only alleviated by lifestyle changes, such as strength training and balance exercises. But it now appears that a new infusion of stem cells from young, healthy people into older people has significantly improved their mobility.
“Frailty is a major source of disability and reduced quality of life for older adults,” says Joshua Hare of Longeveron, a biotechnology company in Miami, Florida. “There is a major 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 altered metabolic processes that cause muscles to contract. The treatment – called laromestrocel – is made from 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.
Following the success of early trials on frailty – which affects around 1 in 4 people aged 65 and over – they have now tested different doses of laromestrocel compared to a placebo in a larger group of 148 people.
The researchers measured how far the participants – aged 74 to 76 and with 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, with no serious safety concerns. For example, those who received the maximum dose were able to walk 41 meters further than those who received the placebo six months after the infusions, reaching 63 meters nine months.
According to the team, laromestrocel inhibits enzymes called matrix metalloproteinases, which have a degenerative effect on structural proteins in blood vessels and other tissues. This means that laromestrocel could regenerate the vascular system, which would then benefit the muscle fibers involved in endurance, Hare explains.
This did not, however, 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.
“It looks very promising,” says Daisy Wilson of the University of Birmingham in the United Kingdom. “I was impressed by the overall change demonstrated in the 6-minute walk time.”
Additionally, the trial may have led to a biomarker for frailty, which could help identify people who will benefit most from treatment – perhaps even before symptoms appear. The researchers looked at a panel of eight potential biomarkers known to be involved in inflammation and blood vessel formation. When analyzing the participants’ blood, they observed that levels of a fragment called sTIE2, which reflects impaired vascular function, gradually decreased with increasing doses of laromestrocel.
This suggests that people with high levels of sTIE2 might benefit more from the therapy, Wilson says. “Frailty is very heterogeneous,” she says. “I think the most important part of geroprotective medicine [interventions that slow the ageing process] moving forward means matching the right patient to the right treatment.
However, it also raised practical concerns about the cost of stem cell therapies and their feasibility. “Given the likely cost of this product, I don’t know how you could justify its use when there have been trials of walking programs, which have improved the 6 minute walk test. [performance] over 50 meters,” she says. “My other thought is how difficult it is to obtain stem cells from volunteers. It would take a lot of volunteers to care for all the fragile people.
Hare counters that various companies are making technological advancements to expand stem cell therapies to reach more people. “There is a lot of work being done regarding the ability to produce this type of stem cell in large quantities, and I am confident that this need will be met,” he says.
Topics:
