A substance that the pancreas secretes can promote the regeneration of the protective nerve-cell coating that is damaged in multiple sclerosis, a mouse study shows.
The substance is fibroblast growth factor 21, or FGF21. It promotes remyelination, the renewal of the myelin sheath protecting the central nervous system, according to the study.
Researchers said the results indicate that scientists may be able to develop a therapy around FGF21 to treat diseases characterized by loss of myelin, including MS.
The study, “Peripherally derived FGF21 promotes remyelination in the central nervous system,” was published in The Journal of Clinical Investigation.
Loss of myelin underlies several neurological diseases. The damage can be repaired with remyelination unless it has reached a certain point, however.
In normal development, what scientists call oligodendrocyte precursor cells become oligodendrocytes, whose major function is generating myelin. When a nervous system injury leads to the depletion of myelin, the precursor cells start to proliferate, the first step in remyelination.
At one point, scientists thought the blood-brain barrier would prevent factors that could contribute to remyelination from reaching the central nervous system. The assumption was that such factors had to originate in the nervous system.
Osaka University researchers hypothesized that neurodegenerative diseases like multiple sclerosis might disrupt the blood-brain barrier.
“Factors in the blood cannot reach the normal brain because CNS [the central nervous system] has the blood-brain barrier,” Professor Rieko Muramatsu said in a press release. “In demyelination diseases like multiple sclerosis, the blood-brain barrier around the lesion is disrupted,” she said the team theorized.
This would allow substances that others organs secreted to reach the brain, they posited.
They tested their theory by injecting mice with a compound called lysophosphatidylcholine that could disrupt the animals’ blood-brain barrier and myelin structures.
The team identified a factor that the pancreas secretes — FGF21 — as a potential candidate for promoting the proliferation of oligodendrocyte precursor cells.
They discovered high levels of FGF21 surrounding the demyelinated lesions of mice treated with lysophosphatidylcholine. They also discovered that leaked FGF21 promoted remyelination. In contrast, remyelination was impaired in mice which lacked FGF21.
“FGF21 is known to regulate metabolism, but its effects on OPC [oligodendrocyte precursor cell] proliferation were unexpected,” Muramatsu said.
Overall, the findings suggested that scientists might be able to build a treatment for demyelinating diseases around FGF21.
FGF21-like substances are already being tested in clinical trials for diabetes, the team noted. If the trials find the treatments safe, the time it takes to develop FGF-21 for other diseases could be shortened, they said.
“There are many drugs that inhibit demyelination, but none that promote remyelination,” Muramatsu said. “FGF21 is a new candidate that deserves more testing. The most important finding is that we show the peripheral milieu [of organs] promotes central nervous system remyelination.”
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