People who develop Parkinson's before 50 may have been born with damaged brain cells, says study
People who develop Parkinson's disease at a young age might have malfunctioning brain cells -- even before birth. A drug used to treat pre-cancers of the skin may help treat the condition, finds a new study. At least 500,000 people in the US are diagnosed with Parkinson's every year, a majority of them over the age of 60. But about 10% of them develop the condition young -- between 21 and 50 years. People develop the disease when the brain nerve cells that make dopamine -- a substance that helps coordinate muscle movement -- malfunction or die. Consequently, these patients experience difficulty moving due to stiff muscles and tremors. Most often, young-onset patients have a family history of Parkinson’s disease.
"Young-onset Parkinson's is especially heartbreaking because it strikes people at the prime of life," said Dr. Michele Tagliati, 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," says Dr Tagliati, co-author of the study.
In this study, the team turned cells from these Parkinson's patients into a kind of stem cell, meaning they turned adult cells into an embryo-like state. These cells can be programmed into developing into any cell types, including muscles, nerves or heart, for instance. The team turned these stem cells into cells that produce dopamine and grew them in their lab.
"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 senior author Dr. Clive Svendsen, director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute and professor of Biomedical Sciences and Medicine at Cedars-Sinai.
When the team observed these cells, they saw an abnormal accumulation of a toxic protein called alpha-synuclein, which is seen in patients with most forms of Parkinson's disease. This accumulation could be the result of malfunctioning "trash cans".
These trash cans of the dopamine-producing cells called lysosomes are tasked with the breaking down and the disposing of proteins - but they failed to do so in young-onset Parkinson's patients. As a result, the toxic protein buildup ends up damaging dopamine-producing cells.
"The cells of the brain cannot dispose of the toxic protein called synuclein – a hallmark of dying neurons in Parkinson’s disease — even before birth. This does not kill the neurons until much later in life though," the researchers tell MEA WorldWide (MEAWW). "Now we know that this starts so early in life we can think about ways to reduce this protein early and use this model as a way to detect whether the Parkinson’s is starting," they add.
Further, the team also tested several drugs that might reverse the abnormality seen in these cells. They found that that one drug, dubbed PEP005, which is already approved by the Food and Drug Administration for treating precancers of the skin, proved effective in lab studies and mice. The drug brought down the levels of the toxic protein.
Encouraged by these positive results in the young-onset patients, the team is now testing whether these findings hold in patients who develop Parkinson's after the age of 50. "While we have shown our drug is effective in this cell model, it needs to be validated in actual patients before it is proven to be a treatment for Parkinson’s. These studies are being planned," they add.
The study has been published in Nature Medicine.