Parkinson’s disease (PD) involves the malfunction and death of vital brain cells, or neurons, in a specific area of the brain called the substantia nigra. The substantia nigra is a production center of a chemical called dopamine, which is important in sending messages to other parts of the brain that control movement and coordination. As the disease progresses, the amount of dopamine produced in the brain decreases, leaving a person unable to control movement normally. At the same time, deposits of sticky proteins, called Lewy bodies, form in the substantia nigra and other brain regions—one of the hallmarks of PD.
Parkinson’s disease is a chronic and progressive movement disorder, meaning that symptoms continue and worsen over time. The cause of PD is unknown, though in rare cases, PD can be caused by genetic mutations or exposure to certain environmental toxins.
As many as one million Americans live with Parkinson’s disease. Approximately 60,000 Americans are diagnosed each year, and this number does not reflect the thousands of cases that go undetected. The incidence of Parkinson’s increases with age, but an estimated four percent of people are diagnosed before the age of 50. Men are one and a half times more likely to have Parkinson’s than women. Although there are treatment options such as medication and surgery to manage the symptoms of the disease, there is presently no cure. The combined direct and indirect cost of Parkinson’s, including treatment, social security payments, and lost income from inability to work, is estimated to be nearly $25 billion per year in the United States alone.
With more than $46 million in funding from Proposition 71 and the California Institute for Regenerative Medicine (CIRM), California’s stem cell scientists are making progress to better understand PD, and to translate those discoveries into new therapies.
Until the advent of pluripotent stem cell technology, there was a bottleneck in the understanding of Parkinson’s disease.
CIRM scientists are taking two general approaches to understand and treat PD. The first approach involves taking skin cells from people with PD, reprogramming them back to pluripotent stem cells, and then coaxing those pluripotent cells to become the type of neuron that is affected by PD. This is known as a stem cell model of the disease. One benefit of this is that scientists can treat these lab-grown, disease-specific neurons with thousands of different drugs to test which ones could be viable therapies in real patients. Because these are cells from the individual patients, there may be patient-specific therapies that could be discovered. There are several CIRM-funded teams throughout the state pursuing this goal.
The second approach involves creating dopamine-producing cells in the lab dish, with the hope that they could replace the neurons that are damaged in people with the disease. Currently, scientists are completing preclinical studies in animals to make sure that the cells are safe and effective. If these studies are successful, clinical trials transplanting the neurons to patients’ brains may be initiated in one or two years. Dopamine neurons produced from embryonic stem cells are also being used to determine whether any existing drugs will slow the death of these neurons, which would give patients a longer time before cell replacement would be necessary. This is the first step in developing a safe therapy for patients with Parkinson’s disease.