Study: Altering reelin levels a possible new treatment for MS

August 14, 2020
A new study suggests decreasing the amount of a protein made in the liver significantly protected against development of the disease’s characteristic symptoms and promoted recovery in an animal model of multiple sclerosis. The findings could lead to a new treatment strategy for this neurological disease and other conditions marked by chronic inflammation.

In 1997, researchers discovered a protein secreted in the brain called reelin. Subsequent work showed reelin appears to help the brain organize itself during development and assist in forming connections between brain cells during adulthood. However, as researchers learned more about reelin, they discovered that large amounts of it are produced in the liver and cells lining blood vessels have receptors for this protein.

Researchers at the UT Southwestern Medical Center investigated this protein’s role in MS. They started by examining blood concentrations of reelin in patients with relapsing-remitting MS. They found that while reelin concentrations were about the same in patients in remission as those without the disease, concentrations were elevated in patients during relapse. These findings suggest that circulating reelin levels might correlate with MS severity and stages, and lowering reelin levels might be a novel way to treat MS.

Investigating further, researchers worked with mice affected by experimental autoimmune encephalomyelitis, a condition that mimics human MS. When these animals were genetically modified so the researchers could control reelin production, they found that eliminating this protein substantially mitigated the disease’s typical paralysis or even eliminated it altogether, in contrast to mice with normal reelin levels. These effects appeared to stem from the lack of monocyte adhesion on the altered animals’ blood vessel walls, which prevented entry into the central nervous system.

The researchers had further success preventing paralysis when unaltered animals with EAE received antibodies that deactivated reelin. This strategy was even effective in animals that already displayed symptoms of the disease – a situation that more closely mimics human patients diagnosed with MS – reducing paralysis severity and promoting healing.

Results of mouse model studies sometimes do not translate to humans and may be years away from being a marketable treatment. However, the researchers suggest that reducing immune cells’ ability to accumulate and cause inflammation by altering reelin levels could represent a new strategy for treating patients with MS.

The findings were published in the journal Science Translational Medicine.

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