One of the most promising prospects for treatment of a neurodegenerative disorder lies in the use of embryonic stem cells to obtain dopamine for Parkinson’s disease. The goal is ambitious, but scientists are coming closer to reaching it, a panel of researchers from around the world said at the Society for Neuroscience meeting.
This new form of treatment, which so far has not been tested in patients, calls for a graft of embryonic stem cells that would give rise to the correct type of neurons in the portion of the midbrain where the cells affected by Parkinson’s disease would normally exist. In addition, they would have to not only produce the neurotransmitter dopamine in the right amounts at the appropriate times, but deliver it to target neurons in the brain that command all the muscles in the body.
In one advance, Anders Björklund and his colleagues at the Wallenberg Neuroscience Center in Lund, Sweden, have identified two genetic sequences that lead embryonic stem cells to develop into dopamine-producing neurons. These neurons form two distinct populations: A9 cells, which will transmit information about movement to the motor neurons that activate muscles throughout the body, and A10 cells, which are involved in the processing of emotions.
Meanwhile, Harvard Medical School researchers led by Ole Isacson have identified a particular protein found on A9 cells but not on A10 cells. That makes it an important marker for scientists interested in treating Parkinson’s disease, because only the A9 cells are involved in the regulation of movement, the main function that is affected by the disease.
But producing exactly the right type of stem cell is not a simple matter of following a recipe in a petri dish; the timing of each step matters as much as the materials.
“You have to remember that when you grow cells in a dish, you are growing them out of context,” Björklund cautioned. Scientists must attempt to replicate the complex chemicals that would be present in the fetus and that normally are “orchestrated precisely, to within hours,” Björklund said.
All too often the cell grafts to be used for treatment include a number of different cell types because it is almost impossible to capture only the needed A9 cells when preparing a graft for implantation. In addition, in order to survive in the patient’s brain, the cells need to have reached a certain age—ideally, 47 days post-conception—but the timing of their growth in the lab cannot be so precisely synchronized.