Turning Stem Cells Into Brain Cells To Cure Multiple Sclerosis And Cerebral Palsy

Lawrence LeBlond for redOrbit.com – Your Universe Online

The painful, debilitating symptoms associated with myelin disorders, such as multiple sclerosis and cerebral palsy, may one day be avoided if new breakthroughs in medical science have anything to say about it. One such breakthrough by a team of scientists at Case Western Reserve School of Medicine (CaseMed) has discovered a technique that directly converts skin cells into a type of brain cells destroyed in patients with these myelin disorders.

The breakthrough, revealed in a paper published in today´s issue of the journal Nature Biotechnology, enables “on demand” production of myelinating cells, which insulate and protect neurons and also enables delivery of brain impulses to the body. In patients with multiple sclerosis, cerebral palsy and other similar disorders, these myelinating cells are destroyed and cannot be replaced.

In the research lab, Paul Tesar, PhD, assistant professor of genetics and genome sciences at CaseMed, and his colleagues used a new technique involving converting fibroblasts — an abundant structural cell in the skin and most organs — into oligodendrocytes, the type of cell responsible for myelinating the neurons of the brain.

This is alchemy on the cellular level, Tesar noted. “We are taking a readily accessible and abundant cell and completely switching its identity to become a highly valuable cell for therapy.”

Using “cellular reprogramming,” the team manipulated the levels of three naturally occurring proteins to induce fibroblast cells to become precursors of oligodendrocytes (oligodendrocyte progenitor cells, or OPCs). With the new method, the team was able to rapidly generate billions of these induced OPCs, and then show that they could regenerate new myelin coatings around nerves after being transplanted in mice.

Tesar and his colleagues, co-first authors Fadi Najm and Angela Lager, report that this new technique, effectively conducted in mice, could hopefully be used someday to treat human myelin disorders. Currently, cures require the myelin coating to be regenerated by replacement oligodendrocytes. But previously, OPCs and oligodendrocytes could only be obtained from fetal tissue or pluripotent stem cells, which were costly procedures and only offered limited benefits.

“The myelin repair field has been hampered by an inability to rapidly generate safe and effective sources of functional oligodendrocytes,” explained study co-author and myelin expert Robert Miller, PhD, professor of neurosciences at CaseMed and the university’s vice president for research. “The new technique may overcome all of these issues by providing a rapid and streamlined way to directly generate functional myelin producing cells.”

The next critical step in the research will be to effectively demonstrate the efficacy and safety of using human cells in the lab setting for myelin research. If the technique can prove successful, it will undoubtedly have widespread consequences for those suffering from debilitating myelin disorders. Therapeutic applications could be far-reaching.

Tesar and colleagues´ research was supported by funding from the National Institute of Health (NIH), the New York Stem Cell Foundation (NYSCF), and the Mt. Sinai Health Care Foundation, as well as Case Western Reserve University School of Medicine.