Oligodendrocyte precursor cells, which normally turn into oligodendrocytes that play a role in producing new myelin, can instead turn into astrocytes and produce scar tissue in the presence of fibrinogen, a blood-clotting protein that leaks into the brain in multiple sclerosis (MS). This is according to the findings of a new study by researchers at the University of California published in Brain.
The researchers hypothesized that this toxic environment in the brain could be why drugs that promote the formation of new myelin in laboratory-based studies may not be efficient in patients with MS.
In order to test their hypothesis, the team led by Katerina Akassoglou, PhD, developed a new method to screen potential new MS drugs in the presence of fibrinogen.
Mark Petersen, MD, the first author of the study, stated, “None of the drugs we tested could reverse the effect of fibrinogen.”
Read more about MS pathophysiology
The researchers then tested other compounds using their newly developed method. They identified a small molecule that could transform oligodendrocyte precursor cells into myelin-producing oligodendrocytes instead of scar tissue-producing astrocytes. When they tested the small molecule in mouse models of MS, the researchers found that it not only increased the production of myelin, but it also prevented paralysis in the animals.
“This compound completely overcame the effect of fibrinogen and restored myelin repair around leaky blood vessels,” Dr. Petersen said. He added that even if treatment started after the animals were sick, they improved and showed signs of faster myelin repair and less nervous system damage.
Similar compounds to the one identified by the researchers of this study are already being tested in clinical trials for other diseases and appear to be safe, suggesting that the new compound could be tested in patients with MS much sooner than other potential drugs that still require many steps before they can be tested in humans.
Langelier J. Overcoming obstacles to promote repair in multiple sclerosis. Gladstone Institutes. August 24, 2021. Accessed September 3, 2021.
Petersen MA, Tognatta R, Meyer-Franke A, et al. BMP receptor blockade overcomes extrinsic inhibition of remyelination and restores neurovascular homeostasis. Brain. Published online August 24, 2021. doi:10.1093/brain/awab106