Researchers at the University of Rochester Medical Center (URMC) say that astrocytes may offer a new approach to the treatment of Parkinson’s disease. Their study (“Delayed transplantation of precursor cell-derived astrocytes provides multiple benefits in a rat model of Parkinsons”) demonstrates that a single therapy could simultaneously repair the multiple types of neurological damage caused by Parkinson's, providing an overall benefit that has not been achieved in other approaches, the scientists add.
“One of the central challenges in Parkinson’s disease is that many different cell types are damaged, each of which is of potential importance,” said Chris Proschel, Ph.D., an assistant professor of biomedical genetics at URMC and lead author of paper. “However, while we know that the collective loss of these cells contributes to the symptoms of the disease, much of the current research is focused on the recovery of only one cell type.”
While Parkinson’s is associated with the loss of dopaminergic neurons–which produce the neurotransmitter dopamine–the disease’s impact is actually far more complex and wide-ranging, disrupting basic signaling functions and triggering the destruction of several other types of cells found in the brain, according to the research team. Consequently, while the preservation and restoration of dopamine producing neurons is critical to slowing or reversing the course of the disease, it is increasingly clear that any successful long-term therapy must both protect the areas of the brain under attack and foster the repair of not only dopaminergic neurons but also the damage that occurs in other cell populations, noted Dr. Proschel.
Using human brain cells, he and his colleagues isolated glial precursors. Through the manipulation of culture conditions and cell signals, the researchers induced the precursor cells to produce a specific class of astrocytes.
While astrocytes tend to garner far less attention than neurons they nevertheless are critical to maintaining a healthy environment in the brain. Scientists are learning that astrocyte dysfunction can contribute to multiple neurological disorders. In both instances, the ability to realize the therapeutic implications of these discoveries has proven to be difficult.
When the astrocytes were implanted into the brains of rats with Parkinson’s disease, the new cells acted similar to astrocytes found in the developing brain, which are more effective at building connections between nerves and creating a suitable environment for growth and repair. Consequently, the implanted astrocytes acted like a repair crew, restoring the health and stability of the structure and allowing the brain's nerve cells to recover and resume normal activity, explained Dr. Proschel.
“Delayed GDABMP [astrocyte] transplantation into the 6-hydroxydopamine lesioned rat striatum restored tyrosine hydroxylase expression and promoted behavioral recovery,” wrote the investigators. “GDABMP transplantation also rescued pathological changes not prevented in other studies, such as the rescue of parvalbumin+ GABAergic interneurons. Consistent with expression of the synaptic modulatory proteins thrombospondin-1 and 2 by GDAsBMP, increased expression of the synaptic protein synaptophysin was also observed. Thus, GDAsBMP offer a multimodal support cell therapy that provides multiple benefits without requiring prior genetic manipulation.”
“The central importance of this work is in revealing a potentially new cell therapy, for which appropriate human cells are in hand, that can be used to restore multiple neuronal populations and to rescue the molecular machinery critical in communication between nerve cells even when cells are transplanted after the damage is already established,” said Mark Noble, Ph.D., the director of the URMC Stem Cell and Regenerative Medicine Institute and a co-author of the study.