Could Parkinson's disease start before birth? A new study certainly seems to suggest so.
Researchers at Cedars-Sinai Medical Center in Los Angeles have shown that people who develop Parkinson's disease before age 50 may have been born with unusual brain cells. While the abnormal brain cells can go undetected for decades, they could explain why some people go on to develop young-onset Parkinson’s disease.
Parkinson's disease is a degenerative disorder of the central nervous system that is associated with shaking, a stooped posture, slowness of movement, and difficulty walking. It’s referred to as early-onset, or young-onset if people develop these symptoms before the age of 50 and accounts for around 10 percent of all cases.
The general underlying cause of the condition is unknown, but it’s thought to have something to do with neuron failure due to the buildup of proteins in the brain cells.
Reporting in the journal Nature Medicine this week, researchers generated a specific type of stem cell, called iPSC, from the blood cells of patients with young-onset Parkinson's disease, a process that takes adult cells "back in time" to a primitive embryonic state. Acting as the body's master cells, the iPSC can go on to develop into any cell type of the human body, while remaining genetically identical to the patient's own cells.
This nifty process allowed the team to create dopamine neurons from each patient and use them to study the brain cells in a petri dish, giving insights into how they function during embryonic development.
"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," Clive Svendsen, senior author and professor of Biomedical Sciences and Medicine at Cedars-Sinai, said in a statement.
Analysis of the dopamine neurons showed they featured dysfunctional lysosomes, the cell organelle responsible for breaking down proteins using digestive enzymes. In turn, this appeared to result in an accumulation of alpha-synuclein, a protein linked to many types of Parkinson’s disease. This suggests that the build-up of alpha-synuclein proteins starts before birth or at least has its origins during embryonic development.
"What we are seeing using this new model are the very first signs of young-onset Parkinson’s," said Svendsen. "It appears that dopamine neurons in these individuals may continue to mishandle alpha-synuclein over a period of 20 or 30 years, causing Parkinson’s symptoms to emerge."
Promisingly, the idea also found one drug that was able to reduce levels of excess alpha-synuclein proteins in dopamine neurons, both in the petri dish and in lab mice. Better still, the drug, known as PEP005, is already approved by the Food and Drug Administration for treating precancers of the skin. However, it’s uncertain how effective it would be at tackling this problem in humans with early-onset Parkinson's.
"Young-onset Parkinson’s is especially heartbreaking because it strikes people at the prime of life,” added Michele Tagliati, 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."