A number of neurological diseases, such as multiple sclerosis, end up with damaged oligodendrocytes that make myelin that in turn protects axons of nerve cells.
The consequences are debilitating and cause all kinds of terrible side effects, but researchers at Caltech have developed a therapy, so far tested in a mouse model, that can help replace damaged oligodendrocytes.
Details from the announcement:
The therapy uses leukemia inhibitory factor (LIF), a naturally occurring protein that was known to promote the self-renewal of neural stem cells and to reduce immune-cell attacks to myelin in other MS mouse models.
“What hadn’t been done before our study was to use gene therapy in the brain to stimulate these cells to remyelinate,” says Paul Patterson, the Biaggini Professor of Biological Sciences at Caltech and senior author of the study.
According to the researchers, LIF enables remyelination by stimulating oligodendrocyte progenitor cells to proliferate and make new oligodendrocytes. The brain has the capacity to produce oligodendrocytes, but often fails to prompt a high enough repair response after demyelination.
“Researchers had been skeptical that a single factor could lead to remyelination of damaged cells,” says Deverman. “It was thought that you could use factors to stimulate the division and expansion of the progenitor population, and then add additional factors to direct those progenitors to turn into the mature myelin-forming cells. But in our mouse model, when we give our LIF therapy, it both stimulates the proliferation of the progenitor cells and allows them to differentiate into mature oligodendrocytes.”
In other words, once the researchers stimulated the proliferation of the progenitor cells, it appeared that the progenitors knew just what was needed—the team did not have to instruct the cells at each stage of development. And they found that LIF elicited such a strong response that the treated brain’s levels of myelin-producing oligodendrocytes were restored to those found in healthy populations.
The researchers note, too, that by placing LIF directly in the brain, one avoids potential side effects of the treatment that may arise when the therapy is infused into the bloodstream.
Caltech statement: Caltech Researchers Develop Gene Therapy to Boost Brain Repair for Demyelinating Diseases
Abstract in The Journal of Neuroscience: Exogenous Leukemia Inhibitory Factor Stimulates Oligodendrocyte Progenitor Cell Proliferation and Enhances Hippocampal Remyelination
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