Parkinson's could appear before birth

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Parkinson's is a common neurodegenerative disease that affects more than six million people worldwide. It is usually diagnosed in people who are 60 years old or older but about 10% of patients diagnosed with the disease are between 21 and 50 years old, according to a case study based on the United States. It is precisely this smaller population that is the focus of a new study on Parkinson's that has recently been published in the journal Nature Medicine.

What the group of researchers from the prestigious American hospital Cedars-Sinai has discovered is that people who suffer from Parkinson's before the age of 50 could have been born with disordered brain cells that were not detected for decades. The researchers have proposed a drug that could potentially help correct the disease processes.

Parkinson's disease (PD) was first described by Dr James Parkinson in 1817 as "trembling paralysis". It is a chronic, progressive neurodegenerative disease that occurs when dopaminergic neurons a substance that helps coordinate muscle movements, are affected or die. The most visible symptoms of Parkinson's are tremors, slowness of movement, muscle stiffness and loss of balance. There is currently no known cure for it and the exact cause is not known.

The present study was conducted by generating special stem cells called induced pluripotent stem cells (IPSC) from cells of patients who had developed the disease at a young age. The process would be similar to having these cells go back in time to an early embryonic state. IPCs are capable of producing any cell type in the human body, all of which are genetically identical to the patient's own. With CMPI, researchers produced dopaminergic neurons, cultured them in the laboratory and analyzed how they worked.


"Our technique allowed us to go back in time to see how well dopaminergic neurons could have worked from the beginning of a patient's life," said lead study author Clive Svendsen, director of the Cedars-Sinai Board of Governors Institute for Regenerative Medicine and professor of Biomedical Sciences and Medicine at the same centre.

The researchers detected two key abnormalities in the dopaminergic neurons they had grown. On the one hand, a protein that is produced in most cases of Parkinson’s called alpha-syneclein, was accumulating. On the other hand, they found lysosomes (cellular structures that act as wastebaskets for the cell to break down and get rid of proteins) that were malfunctioning. This disruption could be the cause of the alpha-synuclein build-up.

"What we're seeing using this new model are the first signs of a young Parkinson's," Svendsen said. "It appears that the dopaminergic neurons in these individuals may continue to mishandle alpha-synuclein over a period of 20 or 30 years, causing the Parkinson's symptoms to appear.


The researchers also found that a drug used to treat skin precancers reduces high levels of alpha-synuclein in both cultured dopamine neurons and laboratory mice.


The next steps are aimed at finding a way for this drug gel to reach the brain as well as determining that the abnormalities seen in the neurons of young Parkinson's patients are in other forms of the disease.

References: A. H. Laperle, S. Sances, N. Yucer, V. J. Dardov, V. J. Garcia, R. Ho, A. N. Fulton, M. R. Jones, K. M. Roxas, P. Avalos, D. West, M. G. Banuelos, Z. Shu, R. Murali, N. T. Maidment, J. E. Van Eyk, M. Tagliati, C. N. Svendsen. iPSC modeling of young-onset Parkinson's disease reveals a molecular signature of disease and novel therapeutic candidates. Nature Medicine, 2020; DOI: 10.1038/s41591-019-0739-1

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