New research coming from Cedars-Sinai suggests that people who are younger than 50 and develop Parkinson’s disease might have been born with disordered brain cells. Those cells go undetected for decades, and the person inflicted shows no sign of illness. When the researchers discovered this, they also found a drug that could potentially correct the disease processes and curb the onset of early-onset Parkinson’s. The study has been published in the journal Nature Medicine.
Dopamine is a chemical substance naturally found in the body that helps coordinate muscle movements, among other things. When brain neurons that make dopamine become impaired or die, Parkinson’s occurs. Symptoms begin as very mild tremors, rigid muscles, slowness of movement, and loss of balance – which get progressively worse. There is no cure yet and no exact explanation for the cause of neuron failure.
Every year, 500,000 people or more are diagnosed with Parkinson’s in the United States alone, and the number continues to rise. Most patients are above 60 years old. Only around 10% are between the ages of 21 and 50 when diagnosed. Cedars-Sinai’s research focuses on this 10%.
Michele Tagliati, MD, co-author of the study, director of the Movement Disorders Program, as well as Cedars-Sinai’s vice chair and professor in the Department of Neurology, said:
Young-onset Parkinson’s is especially heartbreaking because it strikes people at the prime of life. 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.
The Study
- Specialized stem cells called induced pluripotent stem cells (iPSCs) were generated from blood cells of patients with young-onset Parkinson’s disease. To make the iPSCs, the researchers took the adult blood cells and “rewound” them to a primitive embryonic state.
- The iPSCs are unique because they can produce any cell type of the human body. The researchers wanted iPSCs generated from the participants’ blood because then the new cells the iPSCs created would be genetically identical to the patients’ own cells.
- In this experiment, the team used the iPSCs to produce dopamine neurons.
- Then, they cultured the neurons in a dish and analyzed their functions.
- The team did this process for every patient individually.
Clive Svendsen, Ph.D., senior author of the study, director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute and Cedars-Sinai’s professor of Biomedical Sciences and Medicine:
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.
Two significant abnormalities were detected in the dopamine neurons in the dish:
- The accumulation of a protein called alpha-synuclein – a common occurrence in most forms of Parkinson’s disease.
- Malfunctioning lysosomes – the cell structures that act as “trash cans” where cells can break down and dispose of proteins. It is believed that this malfunction could be why alpha-synuclein build-up.
Svendsen said:
What we are seeing using this new model are the very first signs of young-onset Parkinson’s. It appears that dopamine neurons in these individuals may continue to mishandle alpha-synuclein over 20 or 30 years, causing Parkinson’s symptoms to emerge.
The team took their study a step further by using their iPSC model to test a variety of drugs that could potentially reverse the abnormalities they were observing. One drug bore positive results, it’s called PEP005, and the Food and Drug Administration has already approved it but for treating precancers of the skin. In this case, it reduced the elevated levels of alpha-synuclein in the dopamine neurons in the dish and then later on in laboratory mice as well.
There was another abnormality the team found in the patients’ dopamine neurons—elevated levels of an active version of protein kinase C – an enzyme whose role in Parkinson’s remains a mystery. Interestingly enough, PEP005 also countered this enzyme.
Shlomo Melmed, MB, ChB, the executive vice president of Academic Affairs and Cedars-Sinai’s dean of the Medical Faculty, said:
This research is an outstanding example of how physicians and investigators from different disciplines join forces to produce translational science with the potential to help patients. This important work is made possible by the dual leadership of Cedars-Sinai as both a distinguished academic institution and an outstanding hospital.
The team’s next step is to investigate how PEP005 might be delivered to the brain of patients with young-onset Parkinson’s. They anticipate it could be used to treat or even prevent the disease potentially. At the moment, the drug is available in gel form. Meanwhile, they plan to also study patients with other types of Parkinson’s to see if they share the same abnormalities found in neurons of young-onset Parkinson’s.
