Parkinson's disease (PD) is a movement disorder that occurs when nerve cells, or neurons, in the brain die or become impaired. Normally, these neurons produce an important brain chemical called dopamine, which is a chemical messenger responsible for transmitting signals that produce smooth, purposeful movement.
For the 1.5 million people in the United States who have been diagnosed with PD, current treatments, including drugs and deep-brain stimulation, have significant side effects. Drugs affect all parts of the body, not just the dopamine-producing cells of the brain. Deep-brain stimulation blocks the "no-go" pathway of the brain that inhibits movement and affects how people learn and make decisions; it does not stimulate the "go" pathway that controls movement. The resulting imbalance can lead to compulsive behavior.
Researchers in The University of Arizona College of Medicine's Neuroscience Research Program in Tucson are pursuing several promising paths to find better ways to maintain the delicate balance between the electrical and chemical signals that regulate movement. PD is one of the priority neurodegenerative disorders being studied.
Do the Eyes Have It?
What began as retinal cell biology research to find a way to treat age-related macular degeneration (AMD) has turned into a promising cell transplantation possibility for PD as well. Brian McKay, PhD, a UA assistant professor of ophthalmology and vision science, and cell biology and anatomy, is studying the transplantation of retinal pigment epithelial (RPE) cells not only to replace diseased macular RPE cells in patients suffering from AMD, but also to transplant RPE cells into the brains of patients with Parkinson's.
RPE cells support the neurons of the retina. Although the retina is in the eye, it is directly connected to the brain. RPE cells might help treat PD by slowing the death of the neurons and perhaps helping the neurons function.
The challenge of cells is that, unlike a pill which is manufactured, controlled and reproducible, the cells are alive and unpredictable. UA research is seeking ways to identify cells that will behave predictably prior to transplantation, and to learn more about how the cells facilitate neuron health, survival and function. Researchers are working to answer key questions such as: How do we define a set of values that a batch of cells must have to be useful for transplantation? What do we measure to validate the cells – prior to transplantation? For RPE cells in PD, UA laboratory results suggest pigmented cells are promising. Researchers also have identified a factor released by RPE cells that helps dopamine-producing neurons survive.
The neuroscience researchers hope their lab work will lead to techniques to remove RPE cells from the peripheral retina of PD patients, culture them, then transplant them back into the patients' brains, thereby replacing diseased brain tissue with a new source of dopamine and restoring normal function.
Gene Therapy to Control the Brain's Electrical Activity
Hundreds to thousands of genes line up on different chromosomes to determine physical traits. Each gene has a special job to do. In the case of the brain, genes regulate the electrical activity of cells. The goal of the UA gene therapy study is to identify the gene that will work the best to be injected precisely into a group of neuron cells that are specific to PD. Researchers also are testing different delivery agents to direct the gene to the targeted cells.
The current gene therapy research focus is on the Kir2.3 gene, which was discovered and cloned by Torsten Falk, PhD, a UA assistant professor of neurology who is collaborating with Dr. Scott Sherman, a UA assistant professor of neurology.
"Our research is studying ways to use specially-engineered safe viruses to deliver therapeutic genes in the brain. This approach would allow a 'one-shot' treatment without the hardware and wires needed for deep brain stimulation," says Dr. Sherman.
Researchers working in gene therapy routinely use cloning techniques to make copies of genes that they wish to study. The procedure consists of inserting a gene from one organism, often referred to as "foreign DNA," into the genetic material of a carrier called a vector. Examples of vectors include bacteria, yeast cells, viruses or plasmids, which are small DNA circles carried by bacteria. After the gene is inserted, the vector is placed in laboratory conditions that prompt it to multiply, resulting in the gene being copied many times over.
Who is at Risk for Parkinson's Disease?
Family history is one risk factor; an estimated 16 percent of people with Parkinson's Disease (PD) have a known relative with the disease. Gender and environment are other risk factors. PD strikes about 50 percent more men than women, but the reasons are unclear. While it occurs in people throughout the world, a number of studies have found a higher incidence in developed countries, possibly because of increased exposure to pesticides or other toxins in those countries. One clear risk factor for PD is age. The average age of onset is 60 years, and the incidence rises significantly with increasing age. However, about 5 to 10 percent of people with PD have "early-onset" disease that begins before the age of 50, probably genetic in these cases.
Editors/writers note: Parkinson's research is a major fundraising initiative of the UA College of Medicine (see http://medicine.arizona.edu/news/story.cfm?ID=670). Tours of the Neuroscience Research Program laboratories in the Medical Research Building and interviews with patients can be arranged.