Scientists at CWRU School of Medicine Discover
New Technique that Holds Promise for the Treatment of Multiple Sclerosis and
Cerebral Palsy
Newswise —
Researchers at Case Western Reserve School of Medicine have discovered a
technique that directly converts skin cells to the type of brain cells
destroyed in patients with multiple sclerosis, cerebral palsy and other
so-called myelin disorders.
This
discovery appears today in the journal Nature Biotechnology.
This breakthrough now enables “on demand”
production of myelinating cells, which provide a vital sheath of insulation
that protects neurons and enables the delivery of brain impulses to the rest of
the body. In patients with multiple sclerosis (MS), cerebral palsy (CP), and
rare genetic disorders called leukodystrophies, myelinating cells are destroyed
and cannot be replaced.
The new
technique involves directly converting fibroblasts - an abundant structural
cell present in the skin and most organs - into oligodendrocytes, the type of
cell responsible for myelinating the neurons of the brain.
“Its ‘cellular alchemy,’” explained Paul
Tesar, PhD, assistant professor of genetics and genome sciences at Case Western
Reserve School of Medicine and senior author of the study. “We are taking a
readily accessible and abundant cell and completely switching its identity to
become a highly valuable cell for therapy.”
In a process termed “cellular
reprogramming,” researchers manipulated the levels of three naturally occurring
proteins to induce fibroblast cells to become precursors to oligodendrocytes
(called oligodendrocyte progenitor cells, or OPCs).
Tesar’s team, led by Case Western Reserve
researchers and co-first authors Fadi Najm and Angela Lager, rapidly generated
billions of these induced OPCs (called iOPCs). Even more important, they showed
that iOPCs could regenerate new myelin coatings around nerves after being
transplanted to mice—a result that offers hope the technique might be used to
treat human myelin disorders.
When
oligodendrocytes are damaged or become dysfunctional in myelinating diseases,
the insulating myelin coating that normally coats nerves is lost. A cure
requires the myelin coating to be regenerated by replacement oligodendrocytes.
Until now,
OPCs and oligodendrocytes could only be obtained from fetal tissue or
pluripotent stem cells. These techniques have been valuable, but with
limitations.
“The
myelin repair field has been hampered by an inability to rapidly generate safe
and effective sources of functional oligodendrocytes,” explained co-author and
myelin expert Robert Miller, PhD, professor of neurosciences at the Case
Western Reserve School of Medicine 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.”
This initial
study used mouse cells. The critical next step is to demonstrate feasibility
and safety using human cells in a lab setting. If successful, the technique
could have widespread therapeutic application to human myelin disorders.
“The
progression of stem cell biology is providing opportunities for clinical
translation that a decade ago would not have been possible,” said Stanton
Gerson, MD, professor of Medicine-Hematology/Oncology at the School of Medicine
and director of the National Center for Regenerative Medicine and the UH Case
Medical Center Seidman Cancer Center. “It is a real breakthrough.”
Tomado de newswise.com