People who develop Parkinson's disease at a younger age (before age 50) may have malfunctioning brain cells at birth, according to a study that also identified a drug that may help these patients.
At least 500,000 people in the United States are diagnosed with Parkinson's each year. Most are 60 or older at diagnosis, but about 10% are between 21 and 50.
Parkinson's is a neurological disease that occurs when brain neurons that make dopamine become impaired or die. Dopamine helps coordinate muscle movement.
Symptoms get worse over time and include slow gait, rigidity, tremors, and loss of balance. There is currently no cure.
"Young-onset Parkinson's is especially heartbreaking because it strikes people at the prime of life," said study co-author Dr. Michele Tagliati, director of the Movement Disorders Program at Cedars-Sinai Medical Center in Los Angeles.
"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," he said in a hospital news release.
For the study, Tagliati and colleagues generated special stem cells from the cells of patients with young-onset Parkinson's disease. These stem cells can produce any cell type of the human body. Researchers used them to produce dopamine neurons from each patient and analyzed those neurons in the lab.
The dopamine neurons showed two key abnormalities: buildup of a protein called alpha-synuclein, which occurs in most forms of Parkinson's disease; and malfunctioning lysosomes, structures that act as "trash cans" for the cell to break down and dispose of proteins. This malfunction could result in a buildup of alpha-synuclein, the researchers said.
"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 Clive Svendsen, director of the Cedars Sinai Board of Governors Regenerative Medicine Institute.
"What we are seeing using this new model are the very first signs of young-onset Parkinson's," Svendsen said in the release. "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."
The study was published Jan. 27 in the journal Nature Medicine.
The researchers also tested drugs that might reverse the neuron abnormalities. A drug called PEP005 — already approved by the U.S. Food and Drug Administration for treating precancers of the skin — reduced elevated levels of alpha-synuclein both in mice and in dopamine neurons in the lab.
The investigators plan to determine how PEP005, which is available in gel form, might be delivered to the brain to potentially treat or prevent young-onset Parkinson's.
They also want to find out whether the abnormalities in neurons of young-onset Parkinson's patients also exist in other forms of Parkinson's.