Many Born with Parkinson's and Don't Have Clues for Long

Researchers developed a new treatment for patients who get affected before age 50.

Many Born with Parkinson's and Don't Have Clues for Long
Parkinson Disease
Many Born with Parkinson's and Don't Have Clues for Long

Many Born with Parkinson's and Don't Have Clues for Long.  


Dopamine is a substance in our brain neurons. It helps our muscles to function accordingly. But Parkinson's disease damages the dopamine to be impaired or die. The patients affected with this disease show later symptoms in last stages, including slow movement, tremors, rigid muscles, and balance loss. As the reason why neuron failure caused remains unclear exactly in most of the cases, there is no cure available. 

Every year, nearly 500,000 people are diagnosed with Parkinson's alone in the U.S. The rate is also increasing day by day. Among the affected people, 90% are 60 or older when diagnosed. The remaining 10% age range is 21 to 50 years old. A new study has been published in the Nature Medicine journal, took the young-onset patients as a subject of their research.  

Michele Tagliati works as the Managing Director of the Movement Disorders Program. He is also the Vice-Chairman and Professor currently available in the Department of Neurology at Cedars-Sinai. As a co-author of the study, he says, "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." 

As a part of their study, the team developed specialized stem cells called induced pluripotent stem cells (iPSCs) in young-onset Parkinson's patients' cells. After this process can take the adult cells to a primitive embryonic state. The iPSCs are capable of any human body cell. Besides, these cells are also identical to the patients' cells genetically. The researchers used iPSCs to generate dopamine neurons. After that, they cultured them for further analysis in neuron functions. 

A senior author of the study is Clive Svendsen. He serves as the director of the Cedars-Sinai Board. He is a Biomedical Sciences and Medicine professor working there. He says, "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."

While analyzing the dopamine neurons in the dish, the team found two unusual ties. 

First one is the accumulation of alpha-synuclein. In most of the Parkinson's disease cases, alpha-synuclein protein's accumulation is widespread. 

The second one is the lysosomes' malfunctioning. When any break down and dispose of proteins occur in a cell, lysosomes acts as a trash can. This malfunction helps alpha-synuclein protein's healthy growth. Svendsen says, "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 a period of 20 or 30 years, causing Parkinson's symptoms to emerge."  

The team also performed a series of tests on different drugs by using their iPSC model. The drugs may reverse the mentioned unusualities in the dopamines. PEP005 is a kind of medicine previously used to treat precancers of the skin. The Food and Drug Administration approved this drug earlier. PEP005 helped elevate alpha-synuclein levels. The researchers saw its positive effects on both in the dopamines in the dish testing and those of the mice in the laboratory.  

This drug was also helpful in countering another abnormality found in affected dopamine neurons. That is, elevating the protein kinase C, an enzyme version that remains active in the dopamine neurons. The team is not clear of what this enzyme version does with Parkinson's.  

PEP005 is a drug in gel form. As a next step, Tagliati and his team are willing to continue their research so that they might deliver the drugs in the brain to treat or prevent Parkinson's in young-onset patients. They also search for whether the abnormalities occurred in the young-onset Parkinson's patients can occur in other forms of Parkinson's.

Cedars-Sinai's executive vice president working in the Academic Affairs and Dean in the Medical Faculty; Shlomo Melmed is an important member of the research team. He says, "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."   

Other members of the team are from Svendsen's laboratory. The co-authors include Alexander Laperle, Samuel Sances, and Nur Yucer. All of them are PhDs. The Regenerative Medicine Institute and Neurology's involvement was on the top list with others. Others include the Center for Bioinformatics and Functional Genomics, Samuel Oschin Comprehensive Cancer Institute, the Department of Biomedical Sciences, Smidt Heart Institute, the Research Division of Immunology at Cedars-Sinai, along with UCLA.