Parkinson’s disease is a degenerative brain disorder in which a specific type of nerve cell dies off over time.
These specific nerve cells are called dopaminergic neurons, as they produce a chemical molecule called dopamine, which is used for the communication between cells. These neurons are located in a brain region called the substantia nigra, which plays a role in regulating movements. The main symptoms, therefore, include shaking, muscle stiffness, and something that is called bradykinesia, where movements become very slow.
The exact reasons why these cells die are not fully understood; however, there is considerable evidence that a specific protein called alpha-synuclein within these cells becomes toxic. As a result, the cells accumulate the toxic protein into clumps (aggregates), which are thought play a role in the progression and perhaps even initiation of the disease. The disease process and cell death can so far not be reversed or halted. However, symptomatic relief can be obtained by giving a drug that provides the brain with dopamine, which can make up for the loss of dopaminergic neurons. It is important to know that this treatment only works in the early stages of the disease, and as Parkinson’s progresses the brain can lose its responsiveness to the drug.
The fact that the majority of the problems is due to the loss of one specific cell type in a small area of the brain implies that Parkinson’s could potentially be treated with a cell therapy treatment.
Work at CRM
- Dr Tilo Kunath generates dopaminergic cells from clinical-grade human embryonic stem cells (hESCs) as part of an international consortium to bring cell therapy for Parkinson’s to the clinic. Dr Kunath is also working to shed light on the disease mechanisms; he uses cells from Parkinson’s disease patients and turns them into induced pluripotent stem (iPS) cells. In this case, the cells carry a genetic defect in alpha-synuclein that directly causes the disease. These iPS cells are then used to produce nerve cells similar to those that die in the brain of Parkinson’s patients. Growing the cells in a dish enables Dr Kunath and his team to observe the formation of protein aggregates, identify the behaviour of the protein that is damaging to the cells, and also to use them to screen for drugs that can interfere with this process and prevent cell death.