A New Approach Might Be Used To Treat Parkinson's Disease
Written By: Nayada Deevisetpunt
July 5, 2020
Most strategies for treating Parkinson’s disease focus on protecting vulnerable neuronal circuits or preventing neuronal loss. However, Dr. Xiang-Dong Fu of the University of California, San Diego and his colleagues discovered an alternative method to this disease: “a potential alternative is to replace lost neurons to reconstruct disrupted circuits.”
Dr. Fu and his team developed a technique aiming to turn astrocytes, brain cells that produce an RNA-binding protein (PTBP1) that prevents them from becoming neurons, into functional dopaminergic nerve cells. Initially, the team wished to create a cell line in which PTB expression is reduced so that they could study the impact on its target genes. “Unexpectedly, such cells initially grew very slowly in culture, and soon stopped growing completely. We kept the cells in our incubator for a few weeks, wishing to obtain sufficient cells for our experiments. To our surprise, all the cells became neurons,” mentioned Dr. Fu. Realizing that something must have happened to allow a “dramatic cell fate switch”, Dr. Fu decided to test among various types of cells and found that upon PTB downregulation, all of the cells became neurons.
The team discovered that by downregulating PTB in astrocytes, they could convert the non-neuronal cells into neurons that could integrate into the existing neural circuits inside the brain. In fact, “we also found that astrocytes in different regions could be reprogrammed into distinct subtypes of neurons that are closely related to the endogenous neurons in different brain areas,” added Dr. Fu. The team started their testing with a mouse model of Parkinson’s disease. They showed that the neurons converted from astrocytes could replace lost dopaminergic neurons and thus restore dopamine levels; this is leading to the complete reversal of Parkinson’s disease phenotype. Moreover, other similar diseases could also be reversed by converting astrocytes to neurons, as Dr. Fu said, “although we demonstrate this new approach in a Parkinson’s disease model, the principle appears to be generally applicable to other neurological disorders.”
However, there is still a lot to do, such as determining the potential toxicity of this approach due to the depletion of astrocytes, before initiating clinical trials on patients. Furthermore, Dr. Fu mentioned about the side effects that could occur and about the differences in brain size. Future researches would need to make sure that new neurons are capable of growing into larger brains and would require testing in non-human primates as well as older animals. Dr. Ernest Arenas of the Karolinska Institute, author of an accompanying News and Views article, mentioned about some issues suggested by Dr. Fu, but also regarded this as “a major step forward towards the development of cell-replacement therapies for neurodegenerative diseases.”
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