People who develop Parkinson's disease before age 50 may be born with defective brain cells. These can go undetected for decades, according to new research from Cedars-Sinai Medical Center in Los Angeles. For this reason, research points to a drug that could potentially help correct these disease processes.
Prevent Parkinson's disease
Parkinson's occurs whenneuronal activity in the brain, which produces dopamine, a substance that helps coordinate muscle movement, is impaired. Symptoms that worsen over time include slow movements, stiff muscles, tremors, and loss of balance. However, in most cases, the exact cause of neuron failure is unclear and there is no known cure.
Although most patients are 60 years or older at the time of diagnosis, about 10% of them are between 21 and 50 years old. The new study looks at these young patients. To carry out the research, the research team created special stem cells. These are the so-called induced pluripotent stem cells (iPS cells), made from cells from patients with early-stage Parkinson's disease.
This process involves adult blood cells returning to a primitive embryonic state. The iPSC cells can then produce any cell type in the human body that is genetically identical to the patient's own cells. The team used these to produce dopamine neurons from each patient. The scientists then cultured the cells in a test tube and analyzed the functions of the neurons. They discovered two important abnormalities in dopamine neurons:
- Accumulation of a protein called alpha-synuclein, which occurs in most forms of Parkinson's disease.
- Failing lysosomes, cellular structures that serve as “trash cans” for the cell to break down and dispose of proteins. This dysfunction can lead to the buildup of alpha-synuclein.
Medical perspectives
The researchers also used their iPS cell model to test a range of drugs that could reverse these observed abnormalities. They found that this one drug, PEP005, already approved by the Food and Drug Administration, reduced elevated alpha-synuclein levels in both dopamine neurons in the dish and in laboratory mice. The drug also counteracted another abnormality they found in the patients' dopamine neurons. These were the increased levels of an active version of an enzyme called protein kinase C. However, the role of this version of the enzyme in Parkinson's is not clear.
For next steps, Tagliati plans to study how PEP005, currently available in gel form, can be delivered to the brain to potentiallyneurological diseasesto treat or prevent in young patients. The team also plans further research to determine whether the abnormalities found in the study's neurons from Parkinson's patients with younger onset are also present in other forms of Parkinson's.
“This studyis a great example of how physicians and researchers from different disciplines work together to develop translational science that can help patients,” said Shlomo Melmed, vice president for academic affairs and dean of Cedar-Sinai School of Medicine. “This important work is made possible by the dual leadership of Cedars-Sinai as a distinguished academic institution and preeminent hospital.”
