Parkinson’s disease is a disease that most affects older people, but new research suggests that Parkinson’s disease may actually exist in the human brain from birth or even earlier. Scientists at Cedars-Sinai have now found that neurons always fail in the brains of young Parkinson’s patients, but it takes 20 to 30 years for symptoms to accumulate. Thankfully, pep005, an earlier drug, could help prevent the disease.
Parkinson’s disease mainly affects the neurons in the brain that produce dopamine, eventually leading to muscle weakness and stiffness, tremors and balance problems. In most cases, the disease is diagnosed in people over 60 years of age, but about 10 per cent of cases occur between the ages of 21 and 50.
In a new study, scientists from Cedars-Sinai set out to investigate whether there were any early warning signs in neurons in patients diagnosed with Parkinson’s disease before the age of 50. To do this, they created induced pluripotent stem cells (IPSCs), which come from young People with Parkinson’s disease and can then be converted into almost any other cell in the body.
The researchers used IPSC to grow dopamine neurons in laboratory dishes. As they watched them develop, the team noticed that the cellular structure, called lysosomes, was failing. These structures are responsible for breaking down unwanted or worn proteins – when they don’t work properly, proteins begin to build up. The team found that more of a protein called alpha-synaptic nucleus protein is associated with many forms of Parkinson’s disease.
Clive Svendsen, senior author of the study, said: “Our technology provides us with a window into how dopamine neurons can function well from the very beginning of a patient’s life. We are using this new model to see the first signs of the ongoing development of Parkinson’s disease. These people’s dopamine neurons appear to continue to mishandle alpha-synaptic nucleoids for 20 or 30 years, leading to the emergence of Parkinson’s disease. “
Next, the team investigated whether the disease could be treated or even prevented. After testing a range of drugs, they found a seemingly promising drug, PEP005, which has been approved by the FDA for treatment of skin cancer. The researchers found that PEP005 could lower levels of alpha-synaptic nucleus protein and another unusually rich enzyme, protein kinase C, whose role in Parkinson’s disease is not known.
The treatment may seem promising, but it currently works only in mice and lab-grown cells, so it doesn’t necessarily translate into human trials. The team plans to continue this work and figure out how to adapt PEP005 to brain use – currently, it can only be used as a local gel for skin cancer.
The study was published in the journal Nature Medicine.