DISEASES OF GLIA
Diseases of glia, including both astrocytes and oligodendrocytes, are among the most prevalent and disabling, yet least appreciated, conditions in neurology.
In recent years, it has become clear that besides the overtly glial disorders of oligodendrocyte loss and myelin failure, such as the leukodystrophies and inflammatory demyelinations, that a number of neurodegenerative and psychiatric disorders may also be causally linked to glial dysfunction, and derive from astrocytic as well as oligodendrocytic pathology.
The relative contribution of glial dysfunction to many of these disorders may be so great as to allow their treatment by the delivery of allogeneic glial progenitor cells (GPCs), the precursors to both astroglia and myelin-producing oligodendrocytes.
Given the development of new methods for producing and isolating these cells from pluripotent stem cells, both the myelin disorders and appropriate glial-based neurodegenerative conditions may now be compelling targets for cell-based therapy. As such, glial cell-based therapies may offer potential benefit to for a broader range of diseases than ever before contemplated, including disorders such as Huntington disease and the motor neuron degeneration of amyotrophic lateral sclerosis, which have traditionally been considered neuronal in nature.
glia progenitor cells
Oligodendrocytes are the sole source of myelin in the adult CNS, and their loss or dysfunction is at the heart of a wide variety of diseases of both children and adults.
In children, the hereditary leukodystrophies accompany cerebral palsy as major sources of neurological morbidity.
In adults, oligodendrocytic loss and demyelination contribute to diseases as diverse as multiple sclerosis, white matter stroke and spinal cord injury.
In addition, demyelination is also noted in degenerative disorders as varied as normal aging, Huntington’s and Alzheimer’s diseases, while oligodendrocytic pathology has been associated with disorders as diverse as ALS and schizophrenia. As a result, the myelin disorders are especially attractive targets for cell-based therapeutic strategies, as are the related disorders of astrocytes and glial progenitor cells that include dysmyelination as part of their presentation.
Several recent studies have supported the readiness with which axons can remyelinate after either congenital or acquired demyelination, if provided myelinogenic cells. Human glial progenitor cells – also referred to as either oligodendrocyte progenitor cells or NG2 cells – can generate both oligodendrocytes and astrocytes, and as such are promising reagents by which to concurrently restore myelin to demyelinated regions of the diseased or injured CNS, while addressing the disorders of astrocytic function that so often attend white matter disease.