While most clinical trials have focused on improved drug therapies, basic research has focused on why these particular neurons die in the first place and on finding ways to regenerate, repair or replace these cells so functioning can be restored (neurogenesis).
Stem cell therapy is very promising because this disease is clearly related to the failure of one specific kind of cell to do its job. It has been proven in both animal models and clinical practice that when dopamine is reintroduced into the central nervous system, the symptoms abate or are reversed. Thus, if stem cells can be coaxed to become dopamine-producing neurons, either before or after transplantation deep inside the brain, full recovery of lost functioning is theoretically possible.
As the clinical research protocols are being progressively refined, scientists are increasingly certain of the principle that stem cells can be successfully transplanted, survive and produce dopamine with expected improvements in motor control and coordination.
Finding a supply source
The major goal of investigators is to generate a source of cells that can be grown in large supply, maintained indefinitely in the laboratory, and differentiated efficiently into dopamine-producing neurons that work when transplanted into Parkinson’s patients.
This goal has motivated scientists to study both embryonic and adult stem cells as alternative sources of dopamine-producing neurons. In laboratories, with the right combination of growth factors, undifferentiated stem cells can be cultivated to a point where they are committed to becoming dopamine neurons. These are then implanted to finish maturing in the brain.
Embryonic cells appear to differentiate into neurons in a more straightforward manner than many other cell types. However, in animal models they appear to carry the risk of developing cancerous tumors. We don’t yet know if adult neural stem cells have the same potential as embryonic stem cells or carry a similar risk.
There are still many unanswered questions. Among those currently being researched are: which stem cells (e.g. embryonic, blood, bone marrow, retina, skin cells) are best for treating Parkinson’s; tracking cell markers to learn which cells survive, multiply and successfully produce dopamine under what conditions; determining the cues that neural stem cells use to differentiate into dopamine-producing cells; decoding signals in the brain environment that allow transplanted cells to survive, integrate and function properly; and, deciding which areas of the brain and whether transplantation or some other method of delivery (e.g. using genes) would yield the best results.
Finding the switch
An alternative to transplantation is mobilizing the brain to reverse the depletion of dopamine-producing nerve cells. Scientists are investigating how the brain turns on its own mechanism for self-repair, possibly involving adult stem cells that reside in certain parts of the brain. The brain’s white matter contains multipotent progenitor cells that can multiply and form all the major cell types of the brain, including neurons. These appear to be remnants of stem cells that existed during fetal brain development that might be coaxed into becoming dopamine-producing cells in a patient suffering from Parkinson’s disease.
This capacity to regenerate relies on growth hormones (neurotrophic factors such as GNDF) and other signaling molecules that help cells survive and grow. Scientists are beginning to understand what fires up a patient’s own stem cells and internal repair mechanism to allow the body to cope with damage from disease or injury. Even transplanted neural cells have a “homing instinct” that leads them to gravitate to exactly that part of the brain that is injured and needs regeneration.