The Skinny on Breakthrough Myelin Sheath Disorders

MYELIN SHEATH DISORDERSIn patients with multiple sclerosis, cerebral palsy, and other rare genetic disorders known as leukodystrophies, the myelin sheath – the fatty covering that acts as an insulator around nerve fiber is progressively destroyed. Without this vital insulation, brain impulses to the rest of the body are lost leading to debilitating symptoms such as loss of muscle tone, movement, gait, speech, vision, hearing, ability to eat, and behavioral changes.

So we were very excited to learn that researchers at Case Western Reserve School of Medicine have discovered a technique that can directly convert skin cells to the type of brain cells destroyed in myelin disorders.

This amazing new technique involves 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,’” explains Paul Tesar, PhD, assistant professor of genetics and genome sciences at Case Western Reserve School of Medicine “We are taking a readily accessible and abundant cell and completely switching its identity to become a highly valuable cell for therapy.”

axons-and-oligodendrocytesIn 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, rapidly generated billions of these induced OPCs (iOPCs). They also 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. “The new technique may overcome all of these issues by providing a rapid and streamlined way to directly generate functional myelin producing cells.”

BC7251-001This 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.

These are exciting times. The progression of stem cell biology is providing therapeutic opportunities that a decade ago would not have been thought possible. As always SRxA’s Word on Health, will bring you further developments on this story as soon as they’re released.

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One thought on “The Skinny on Breakthrough Myelin Sheath Disorders

  1. In an almost simultaneous and equally serendipitous discovery, scientists at The Scripps Research Institute (TSRI) have found a way to turn bone marrow stem cells directly into brain cells.

    Current techniques for turning patients’ marrow cells into cells of some other desired type are relatively cumbersome, risky and effectively confined to the lab dish. The new finding points to the possibility of simpler and safer techniques. Cell therapies derived from patients’ own cells are widely expected to be useful in treating spinal cord injuries, strokes and other conditions throughout the body, with little or no risk of immune rejection.

    “These results highlight the potential of antibodies as versatile manipulators of cellular functions,” said Richard A. Lerner, the Lita Annenberg Hazen Professor of Immunochemistry and institute professor in the Department of Cell and Molecular Biology at TSRI, and principal investigator for the new study. “This is a far cry from the way antibodies used to be thought of—as molecules that were selected simply for binding and not function.”

    The researchers discovered the method, reported in the online Early Edition of the Proceedings of the National Academy of Sciences the week of April 22, 2013, while looking for lab-grown antibodies that can activate a growth-stimulating receptor on marrow cells. One antibody turned out to activate the receptor in a way that induces marrow stem cells—which normally develop into white blood cells—to become neural progenitor cells, a type of almost-mature brain cell.

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