A Cure for Parkinson's?

Neurodegenerative diseases are some of the most insidious diseases known to man. The individual with the disease is only able to watch as their mental state slowly declines until their death. As a country, we spent $789 on neurodegenerative diseases in 2014(Wiley, 2017). It looks like those efforts might have finally paid off. In June, a research lab at the University of California, San Diego (UCSD) published an article in which they were able to completely reverse the effects of Parkinson’s in mice. In Parkinson’s disease, dopaminergic neurons in the substantia nigra die off causing dopamine concentration in the brain to decrease (Bergman, 2002). As a result, the individual with the disease will experience tremors and a decreasing level of control over their body as the disease progresses.

The scientists at UCSD were able to create new dopaminergic neurons from astrocytes by inhibiting the expression of the gene that codes for the RNA binding protein PTB. In astrocytes, the main function of PTB is to stop the cell’s differentiation into a neural cell.  In vitro experiments of both mouse and human astrocytes showed that by blocking PTB expression, astrocytes differentiated into neurons. (Qian et al., 2020). Once it was established that the astrocytes would differentiate into neurons, the scientists injected DNA that induced a knockdown of PTB into the substantia nigra of mice with induced Parkinson’s. Like the in vitro experiments, the astrocytes in the substantia nigra differentiated into neurons capable of producing dopamine. Furthermore, the mice no longer showed the symptoms of Parkinson’s disease, and no additional treatments were needed after the first injection (Qian et al., 2020).

While the results are promising, we are still a long way off from human trials. We know that knockdown of PTB is capable of creating neurons out of astrocytes in humans, and mouse models show it works in vivo. However, a new method of inducing the knockdown must now be created because inducing the knockdown of PTB by injecting a virus vector is not approved in humans. We also do not know if there will be any lasting side effects or how effective the treatment is in humans. That being said, there is still hope that one day knockdown of PTB in human astrocytes will lead to a cure for Parkinson’s disease.

References

 

Bergman, H., & Deuschl, G. (2002, March 28). Pathophysiology of Parkinson's disease: From clinical neurology to basic neuroscience and back. Retrieved from https://onlinelibrary.wiley.com/doi/full/10.1002/mds.10140?casa_token=gqA5MJh63xMAAAAA:W_VXNKR3aOW6TYe5eWDNLa3o418JjRdVhX9StTT-T_ObESykuF_w5LYFOqMoIji29p2zyRmZ33YWgjw

 

Qian, H., Kang, X., Hu, J., Zhang, D., Liang, Z., Meng, F., Zhang, X., Xue, Y., Maimon, R., Dowdy, S. F., Devaraj, N. K., Zhou, Z., Mobley, W. C., Cleveland, D. W., & Fu, X. D. (2020). Reversing a model of Parkinson's disease with in situ converted nigral neurons. Nature, 582(7813), 550–556. https://doi.org/10.1038/s41586-020-2388-4

 

Wiley. (2017, March 28). Neurological diseases cost the US Nearly $800 billion per year. ScienceDaily. Retrieved September 29, 2020 from www.sciencedaily.com/releases/2017/03/170328105855.htm