Drugs that remove worn and damaged immune cells may help treat multiple sclerosis (MS), a study in mice suggests.
MS is a neurodegenerative disease in which the immune system mistakenly attacks the protective coating around nerves, called myelin. It . Most people with the condition have occasional relapses 鈥� where myelin is damaged and their symptoms worsen 鈥� followed by periods of recovery, in which myelin regenerates. This is known as relapsing remitting multiple sclerosis.
As people with MS age, they usually advance into what is called the progressive phase. This is when symptoms continuously worsen without recovery periods, meaning less myelin regenerates, says at Georgetown University in Washington DC.
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To understand why remyelination typically occurs earlier in the disease, but not later, Gross and his colleagues analysed the effects of senescent cells, which accumulate with age. These are cells that have become so worn or damaged they cease to function. Instead of dying, though, they linger in tissues, like cellular zombies. 鈥淏ecause senescence is associated with ageing, we wanted to see if there was an increase in senescent cells with age following demyelination,鈥� says Gross.
First, the researchers damaged myelin in five 3-month-old mice and four 18-month-old mice by injecting a toxin into their spinal cords. They then genetically analysed cells at the site of injury and found, on average, a sixfold increase in a marker of cellular senescence in cells of the older mice compared with those of the younger mice. The increase was greatest in microglia, which are immune cells of the nervous system.
This finding suggests a myelin injury leads to a greater build-up of senescent immune cells in older animals than in younger ones. Further experiments revealed that this increase seemed to impair the animals鈥� ability to regenerate myelin.
To investigate whether targeting senescent immune cells could help repair myelin in old age, the researchers once again injected a toxin into the spinal cords of 11 mice aged 12 months old. They then treated five of them with a drug belonging to a class of medications known as senolytics, which remove senescent cells. The medication in question hasn鈥檛 been approved for use in humans but is currently in clinical trials. The rest of the animals received a sham treatment instead of the senolytic drug.
They found, on average, a 65 per cent greater increase in a protein used to rebuild myelin in treated mice than those in the control group. This suggests that clearing senescent immune cells may enhance myelin regeneration, says Gross, who presented these findings at a in Washington DC.
This could be useful for treating multiple sclerosis, especially in the progressive phase of the disease, when demyelination is most severe. 鈥淎ll the treatments for [multiple sclerosis] treat the autoimmune part,鈥� says Gross. 鈥淚f we can improve that remyelination phase, maybe that鈥檚 another way to attack the problem.鈥�
However, we don鈥檛 know yet if these findings will translate to humans, says at the Mayo Clinic in Minnesota. Further research will be needed to understand if senescent-clearing drugs could be effective at treating the disease in people, he says. Still, 鈥渢his research demonstrates promise for a debilitating disease鈥�, says Baker.
