UC DAVIS (US) — Scientists have discovered a target for the development of drugs and stem cell therapies that could aid in the recovery of patients with multiple sclerosis, cerebral palsy, and stroke.
The study, conducted on mice and published online in the journal Scientific Research, focused on cells in the brain called oligodendrocytes, which surround nerve fibers and provide them with a protective myelin sheath.
Myelin increases the speed at which nerve impulses propagate, similar to the role of insulation around an electric wire, and is essential for the proper functioning of the nervous system.
“We have discovered that enhancing a factor important in early brain development could play a powerful role in healing,” says Wenbin Deng, assistant professor of cell biology and human anatomy at the University of California, Davis.
“This information can be very important for harnessing the regenerative capacity of the brain through drugs or stem cell therapy.”
Researchers studied a factor called Zfp488 that has been found only in oligodendrocytes. Although researchers knew it is required for oligodendrocytes to mature during embryonic development, they were surprised to find it also plays a role in adult brain cells.
For the study, investigators induced demyelination in mice by feeding them a diet containing cuprizone, a chemical that specifically damages mature oligodendrocytes.
After two weeks, one group of mice was injected with a retrovirus that contained the genetic code for Zfp488, causing these mice to express this factor in their cells. After three more weeks on the diet, these mice developed new oligodendrocytes from precursor cells in much greater numbers than occurred in control mice, which were also on the cuprizone diet but were not provided with Zfp488.
The researchers found not only oligodendrocyte recovery, but important differences in motor function between the two groups.
Three days after the diet was stopped, mice provided with Zfp488 performed significantly better on a test of running time than did the controls, and performed as well as mice that never received the demyelinating diet.
This is especially important, because people with a demyelinating disease have poor motor control as a major symptom.
“The fact that Zfp488 not only induced remyelination but also led to restoration of function is very exciting,” Deng says.
“This is a step toward our most important goal of finding a therapy for functional recovery for patients with a demyelinating disorder or injury.”
The study findings could lead to identifying a drug that specifically enhances the activity of Zfp488. Another potential avenue of therapy could be to implant precursor cells of oligodendrocytes to promote regeneration.
“Until this study, we had no clear idea of a target to promote remyelination in demyelinating diseases and injuries,” says co-author David E. Pleasure, professor of neurology and pediatrics. “This knowledge opens up exciting new avenues of research.”
More news from UC Davis: http://www.news.ucdavis.edu/