LivingParkinson's could appear before birth

Parkinson's could appear before birth

Parkinson’s is a common neurodegenarative disease that affects more than six million people around the world . It is usually diagnosed in people who are 60 years or older, but, to take the United States as an example, about 10% of patients diagnosed with the disease are between 21 and 50 years old. It is precisely in this minor population that a new study on Parkinson’s that has recently been published in the journal Nature Medicine is focused.

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 went undetected for decades. They also propose a drug that could potentially help correct disease processes.

Parkinson’s disease (PD) was first described by Dr. James Parkinson in 1817 as a “trembling paralysis.” It is a chronic and progressive neurodegenerative disease that occurs when dopaminergic neurons, which are activated by dopamine, a substance that helps coordinate muscle movements, are affected or die. The most visible symptoms of Parkinson’s are tremors, slow movement, muscle stiffness, and loss of balance. At the moment there is no known cure for it and its cause is not exactly known.

The present study was carried out by generating special stem cells called induced pluripotent stem cells (IPCs) from cells of patients who had developed the disease when they were young. The process would be similar to making these cells go back in time to a primitive embryonic state . CMPIs are capable of producing any type of cell in the human body, all genetically identical to those of the patient himself. Using the CMPIs, the researchers produced dopaminergic neurons, grew them in the laboratory, and analyzed how they worked.

“Our technique allowed us to go back in time to see how well dopaminergic neurons might have functioned early in a patient’s life,” said Clive Svendsen, lead author of the study, director of the Institute for Regenerative Medicine at the Board of Trustees. Governors of Cedars-Sinai and professor of Biomedical Sciences and Medicine at the same center.

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 and is known as alpha-synuclein was accumulating. On the other hand, they found lysosomes (cellular structures that act as a garbage dump for the cell to break down and get rid of proteins) that were malfunctioning. This alteration could be the cause of alpha-synuclein to accumulate.

“What we are 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 to 30 years, causing Parkinson’s symptoms to appear.”

Researchers have also discovered that a drug used to treat skin precancers reduces high levels of alpha-synuclein , both in cultured dopamine neurons and in laboratory mice.

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

 

Referencias: 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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