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Parkinson's disease may start before birth: Stem cell study finds malfunctioning brain cells in patients who were diagnosed before age 50; researchers test potential new treatment:

People who develop Parkinson's disease before age 50 may have been born with disordered brain cells that went undetected for decades, according to new Cedars-Sinai research. The research points to a drug that potentially might help correct these disease processes.

Parkinson's occurs when brain neurons that make dopamine, a substance that helps coordinate muscle movement, become impaired or die. Symptoms, which get worse over time, include slowness of movement, rigid muscles, tremors and loss of balance. In most cases, the exact cause of neuron failure is unclear, and there is no known cure.

At least 500,000 people in the U.S. are diagnosed with Parkinson's each year, and the incidence is rising. Although most patients are 60 or older when they are diagnosed, about 10% are between 21 and 50 years old. The new study, published in the journal Nature Medicine, focuses on these young-onset patients.

"Young-onset Parkinson's is especially heartbreaking because it strikes people at the prime of life," said Michele Tagliati, MD, director of the Movement Disorders Program, vice chair and professor in the Department of Neurology at Cedars-Sinai. "This exciting new research provides hope that one day we may be able to detect and take early action to prevent this disease in at-risk individuals." Tagliati was a co-author of the study.

To perform the study, the research team generated special stem cells, known as induced pluripotent stem cells (iPSCs), from cells of patients with young-onset Parkinson's disease. This process involves taking adult blood cells "back in time" to a primitive embryonic state. These iPSCs can then produce any cell type of the human body, all genetically identical to the patient's own cells. The team used the iPSCs to produce dopamine neurons from each patient and then cultured them in a dish and analyzed the neurons' functions.

[...]"Our technique gave us a window back in time to see how well the dopamine neurons might have functioned from the very start of a patient's life," said Clive Svendsen, PhD, director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute and professor of Biomedical Sciences and Medicine at Cedars-Sinai. He was the study's senior author.

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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