People who develop Parkinson’s disease before age 50 may have been born with disordered brain cells that went undetected for decades, according to new Cedars-Sinai Medical Centre research.
The research points to a drug that potentially might help correct these disease processes.
“Young-onset Parkinson’s is especially heartbreaking because it strikes people at the prime of life,” said Michele Tagliati, MD, 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.”
To perform the study, the research team generated special stem cells – known as induced pluripotent stem cells (iPSCs) – from cells of patients with young-onset Parkinson’s disease.
This process involves taking adult blood cells “back in time” to a primitive embryonic state. These iPSCs can then produce any cell type of the human body, all genetically identical to the patient’s own cells.
The team used the iPSCs to produce dopamine neurons from each patient and then cultured them in a dish and analysed the neurons’ functions.
The researchers detected two key abnormalities in the dopamine neurons in the dish:
- Accumulation of a protein called alpha-synuclein, which occurs in most forms of Parkinson’s disease.
- Malfunctioning lysosomes, cell structures that act as ‘rubbish bins’ for the cell to break down and dispose of proteins. This malfunction could cause alpha-synuclein to build up.
The investigators also used their iPSC model to test a number of drugs that might reverse the abnormalities they had observed.
They found that that one drug called PEP005 – which is already approved by the Food and Drug Administration for treating precancers of the skin – reduced the elevated levels of alpha-synuclein in both the dopamine neurons in the dish and in laboratory mice.
Next, the team plans to investigate how PEP005 – currently available in gel form – might be delivered to the brain to potentially treat or prevent young-onset Parkinson’s.
The team also plans more research to determine whether the abnormalities the study found in neurons of young-onset Parkinson’s patients also exist in other forms of Parkinson’s.
Cedars-Sinai Medical Center, Los Angeles, USA.
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