An intriguing experiment has led researchers to conclude that people who develop early-onset Parkinson’s disease – between the age of 21 and 50 – may have been born with abnormal brain cells that go undetected for decades.
These disordered cells allow gradual accumulation of the α-synuclein protein that forms abnormal deposits in the brain, and dysregulated lysosomal proteins that ordinarily play a role in clearing abnormal proteins from cells.
The researchers from Cedars-Sinai Medical Center say they are investigating an FDA approved skin cancer drug they believe might help correct these abnormalities before they become symptomatic.
In other words, they suggest that early-onset Parkinson’s – the form of the disease that Michael J. Fox was diagnosed with at the age of 29 – may be treatable or even prevented. It’s an astonishing claim.
How did they make this discovery?
To perform the study, the research team generate pluripotent stem cells – master cells that can potentially produce any cell or tissue the body needs to repair itself – from blood cells of three patients with young-onset Parkinson’s disease.
The patients were aged 30-39 and had no known familial history of the disease and no Parkinson’s disease mutations.
When generated in the laboratory, these master cells called induced pluripotent stem cells (iPSCs). In their experiment, the Cedars-Sinai researchers described this process as taking adult blood cells “back in time” to a primitive embryonic state.
The team used the stem cells to produce dopamine neurons from each patient – and then cultured them in a dish and analysed the neurons’ functions.
In Parkinson’s patients, brain neurons that make dopamine – a neurotransmitter that works to coordinate muscle movement – become impaired or die.
“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 Dr Clive Svendsen, PhD, director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute, and the study’s senior author.
According to a statement from Cedars-Sinai, 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 “trash cans” for the cell to break down and dispose of proteins. This malfunction could cause alpha-synuclein to build up.
Watching young-onset Parkinson’s reveal itself
Dr Svendsen said the experiment allowed the researchers “to see 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 investigators went further, using their iPSC to test a number of drugs that might reverse the lab-born abnormalities.
They found that that one drug, PEP005 – already approved by the Food and Drug Administration for treating pre-cancers of the skin – reduced the elevated levels of alpha-synuclein in both the dopamine neurons in the dish and in laboratory mice.
The drug also countered another abnormality they found in the patients’ dopamine neurons – elevated levels of an active version of an enzyme called protein kinase C. However, the role of this enzyme version in Parkinson’s is not clear.
The drug PEP005 is only available in gel form and the researchers plans to investigate “how it might be delivered to the brain to potentially treat or prevent young-onset Parkinson’s.”
Getting hopes up or realistic progress?
In Parkinson’s disease, the symptoms – including slowness of movement, rigid muscles, tremors, loss of balance and impaired mood control – get worse over time. In most cases, the exact cause of neuron failure is unclear, and there is no known cure.
Just about every week, a new insight into the disease is published. Last week, The New Daily reported on new research that found living less than 50 metres from a major road – or less than 150 metres from a highway – has been linked to significantly higher incidence of dementia and Parkinson’s disease.
In 2018, we published an exciting Australian study that suggested – subject to clinical testing – the inflammation of the brain that causes so much of the progressive damage in Parkinson’s disease (PD) could be halted by taking a single pill each day.
Both these studies might eventually prove to be correct. But it’s a long wait for the more than 10 million sufferers worldwide and their families.
This latest study could be a game-changer. But it could just as easily wither on the vine. Still, better to take heart than not.
Most patients are 60 or older when they are diagnosed, about 10 per cent are between 21 and 50 years old. .
“Young-onset Parkinson’s is especially heartbreaking because it strikes people at the prime of life,” said Dr Michele Tagliati, director of the Movement Disorders Program, vice chair and professor in the Department of Neurology at Cedars-Sinai, and co-author of the study.
“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.”