Study suggests Parkinson's present from birth and may be preventable
Parkinson’s disease is an illness that most often affects older people, but new research suggests it may actually be present in the brain right from birth – and even earlier. Scientists from Cedars-Sinai have now found that in the brains of young-onset Parkinson’s patients, malfunctioning neurons are always there but it takes 20 to 30 years for the symptoms to accumulate. Thankfully, a drug that’s already on the market could help prevent the disease from taking hold if caught early enough.
Parkinson’s disease primarily affects neurons in the brain that produce dopamine, eventually causing muscle weakness and stiffness, tremors, and balance problems. Most of the time, the disease is diagnosed in older people over the age of 60, but around 10 percent of cases occur in those aged between 21 and 50.
In a new study, scientists from Cedars-Sinai set out to investigate whether there were any early warning signs in the neurons of patients who’d been diagnosed with Parkinson’s before they turned 50. To do so, they created induced pluripotent stem cells (IPSCs) from young-onset Parkinson’s patients, which can then be turned into almost any other cells in the body.
The researchers used the IPSCs to grow dopamine neurons in lab dishes. As they watched them develop, the team noticed that cell structures called lysosomes were malfunctioning. These structures are responsible for breaking down unneeded or worn-out proteins – so when they don’t work as well as they should, proteins begin to pile up. And one such protein that the team spotted in higher amounts is called alpha-synuclein, which is implicated in many forms of Parkinson’s.
"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,” says Clive Svendsen, senior author of the study. "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.”
Next up, the team investigated whether the condition could potentially be treated or even prevented. After testing a series of drugs, they found one that looked promising – PEP005, which has already been approved by the FDA for use against skin precancers. The researchers found that PEP005 works to reduce the levels of alpha-synuclein, as well as another abnormally-abundant enzyme called protein kinase C, whose role in Parkinson's remains unclear.
The treatment looks promising, but for now it’s only been shown to work in mice and lab-grown cells, so it won’t necessarily translate to human trials. The team plans to continue working on this, as well as figuring out how to adapt PEP005 for use in the brain – at the moment, it’s only available as a topical gel, since it's for treating skin cancer.
The research was published in the journal Nature Medicine.