An international team of scientists has recently reported on their findings of successfully reducing the symptoms and slowing the progression of Huntington's disease in mice using healthy human brain cells. The investigators implanted animals with human glial cells derived from stem cells. One of the roles of glia is to tend to the health of neurons, and the results from this new study reveal that replacing sick mouse glia with healthy human cells blunted the progress of the disease and rescued nerve cells at risk of death.
“The role that glia cells play in the progression of Huntington's disease has never really been explored,” explained senior study author Steve Goldman, M.D., Ph.D., co-director of the University of Rochester Center for Translational Neuromedicine and professor at the Center of Basic and Translational Neuroscience at the University of Copenhagen. “This study shows that these cells are not only important actors in the disease but may also hold the key to new treatment strategies.”
“It's the first time, we've conducted this type of transplant, and the results are both positive and surprising,” Dr. Goldman added. “It reveals that diseased mice injected with healthy glia cells live longer, and their condition improves. This is very promising, and it's only the tip of the iceberg. We hope to be able to conduct further research on whether this method could possibly result in a treatment for Huntington's.”
Huntington's is a hereditary neurodegenerative disease that is most closely characterized by the loss of a specific nerve cell in the brain—the medium spiny neuron—that plays a critical role in motor control. Over time, the disease results in involuntary movements, problems with coordination, and cognitive decline and depression. Currently, there is no way to slow or modify this fatal illness.
Researchers have observed that medium spiny neurons in the striatum—the area of the brain most affected by Huntington’s—die as a result of the disease and that neighboring glial cells, called astrocytes, also become sick and do not function properly. However, it had not been previously elucidated if the sick astrocytes contributed to the signs and symptoms of the disease.
The research team was able to conduct a series of experiments in which they isolated human glial progenitors—those cells in the central nervous system that give rise to astrocytes—from both embryonic stem cells and brain tissue and implanted the cells into the striatum of mice with Huntington's disease. Consistent with prior studies, the researchers observed that the resulting human astrocytes outcompeted the native glial cells, resulting in mice with native neurons but human glia.
The findings from this study were published recently in Nature Communications in an article entitled “Human Glia Can Both Induce and Rescue Aspects of Disease Phenotype in Huntington Disease.”
Additionally, the scientists uncovered that human glial cells transplanted into mice with the Huntington's disease mutation appeared to keep neurons healthier and extended the animals' survival. They also conducted a battery of tests designed to measure the animals' behavior, memory, and motor skills, and the mice with healthy human glia performed significantly better than untreated mice with Huntington's disease.
“This is at least in part due to the fact that glia cells control the level of potassium in the brain, which is vital for our motor and cognitive skills,” Dr. Goldman noted. “In Huntington disease, the level of potassium in brain tissue becomes unstable, but when the glia cells are injected they restore potassium to normal levels. We hope that as we continue our research on these mechanisms in the future, that it will bring us closer to finding a meaningful treatment for Huntington's, and possibly other similar neurodegenerative diseases.”
Conversely, when healthy mice were implanted with human glia carrying the genetic mutation that causes Huntington's, the animals exhibited symptoms of the disease.
Because glial cells have been shown to migrate and proliferate throughout the brain once implanted, the research team believes their recent findings could herald a potential new approach to rescue nerve cells threatened by the disease.
“The partial rescue of deficiencies we observed in this study tells us that there is a significant glial component in Huntington's disease and that we may be able to improve function and delay progression with glial transplants,” Dr. Goldman concluded.