Parkinson’s disease may start before birth, study suggests

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People who develop Parkinson’s disease before the age of 50 may have been born with disordered brain cells, new research suggests.

Scientists say the abnormalities may have gone undetected for years.

They add that their findings may point to a drug which could potentially help correct the process.

Parkinson’s occurs when neurons in the brain that make dopamine – a substance that helps co-ordinate muscle movement – become impaired or die.

Symptoms include slowness of movement, rigid muscles, tremors, and loss of balance.

In most cases, why the neuron fails is unknown, and there is no known cure.

Study senior author Dr Clive Svendsen, director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute and professor of biomedical sciences and medicine at Cedars-Sinai, said: “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.”

Researchers generated special stem cells, known as pluripotent stem cells (iPSCs), from cells of patients with young-onset Parkinson’s.

This involved taking adult blood cells back to a primitive embryonic state.

The stem cells could then produce any cell type of the human body, all genetically identical to the patient’s own.

The scientists detected two key abnormalities in the dopamine neurons in the dish.

One was the accumulation of a protein called alpha-synuclein, which occurs in most forms of Parkinson’s disease.

The other was malfunctioning lysosomes – cell structures that act as bins for the cell to break down and dispose of proteins.

This malfunction could cause alpha-synuclein to build up.

Dr 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 a period of 20 or 30 years, causing Parkinson’s symptoms to emerge.”

Researchers also tested a number of drugs, to see whether they could reverse the observed abnormalities.

They found that that one drug, PEP005, which is already approved in America 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.

Next the team plan to investigate how the drug – which is currently available in gel form – might be delivered to the brain to potentially treat Parkinson’s.

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