In recent years, research on Parkinson's has advanced to the point that halting the progression of the disease, restoring lost function, and even preventing the disease are all considered realistic goals. While the goal of preventing Parkinson's disease may take years to achieve, researchers are making great progress in understanding and treating it.
One of the most exciting areas of Parkinson's research is genetics. Studying the genes responsible for inherited cases can help researchers understand both inherited and sporadic cases of the disease. Identifying gene defects can also help researchers
- understand how Parkinson's occurs
- develop animal models that accurately mimic the death of nerve cells in humans
- identify new approaches to drug therapy
- improve diagnosis.
Researchers funded by the National Institute of Neurological Disorders and Stroke are gathering information and DNA samples from hundreds of families with members who have Parkinson's and are conducting large-scale studies to identify gene variants that are associated with increased risk of developing the disease. They are also comparing gene activity in Parkinson's with gene activity in similar diseases such as progressive supranuclear palsy.
In addition to identifying new genes for Parkinson's disease, researchers are trying to learn about the function of genes known to be associated with the disease, and about how gene mutations cause disease.
Effects of Environmental Toxins
Scientists continue to study environmental toxins such as pesticides and herbicides that can cause Parkinson's symptoms in animals. They have found that exposing rodents to the pesticide rotenone and several other agricultural chemicals can cause cellular and behavioral changes that mimic those seen in Parkinson's.
Role of Lewy Bodies
Other studies focus on how Lewy bodies form and what role they play in Parkinson's disease. Some studies suggest that Lewy bodies are a byproduct of a breakdown that occurs within nerve cells, while others indicate that Lewy bodies are protective, helping neurons "lock away" abnormal molecules that might otherwise be harmful.
Biomarkers for Parkinson's -- measurable characteristics that can reveal whether the disease is developing or progressing -- are another focus of research. Such biomarkers could help doctors detect the disease before symptoms appear and improve diagnosis of the disease. They also would show if medications and other types of therapy have a positive or negative effect on the course of the disease. The National Disorders of Neurological Disorders and Stroke has developed an initiative, the Parkinson’s Disease Biomarkers Identification Network (PD-BIN), designed specifically to address these questions and to discover and validate biomarkers for Parkinson’s disease.
Researchers are conducting many studies of new or improved therapies for Parkinson's disease. Studies are testing whether transcranial electrical polarization (TEP) or transcranial magnetic stimulation (TMS) can reduce the symptoms of the disease. In TEP, electrodes placed on the scalp are used to generate an electrical current that modifies signals in the brain's cortex. In TMS, an insulated coil of wire on the scalp is used to generate a brief electrical current.
A variety of new drug treatments for Parkinson's disease are in clinical trials. Several MAO-B inhibitors including selegiline, lazabemide, and rasagiline, are being tested to determine if they have neuroprotective effects in people with Parkinson’s disease.
The National Institute of Neurological Disorders and Stroke has launched a broad effort to find drugs to slow the progression of Parkinson's disease, called NET-PD or NIH Exploratory Trials in Parkinson's Disease. The first studies tested several compounds; one of these, creatine, is now being evaluated in a larger clinical trial. The NET-PD investigators are testing a highly purified form of creatine, a nutritional supplement, to find out if it slows the decline seen in people with Parkinson's. Creatine is a widely used dietary supplement thought to improve exercise performance. Cellular energy is stored in a chemical bond between creatine and a phosphate.
More recently, NET-PD has initiated pilot studies to test pioglitazone, a drug that has been shown to stimulate mitochondrial function. Because mitochondrial function may be less active in Parkinson’s disease, this drug may protect vulnerable dopamine neurons by boosting mitochondrial function.
Another potential approach to treating Parkinson's disease is to implant cells to replace those lost in the disease. Starting in the 1990s, researchers conducting a controlled clinical trial of fetal tissue implants tried to replace lost dopamine-producing nerve cells with healthy ones from fetal tissue in order to improve movement and the response to medications. While many of the implanted cells survived in the brain and produced dopamine, this therapy was associated with only modest functional improvements, mostly in patients under the age of 60. Some of the people who received the transplants developed disabling dyskinesias that could not be relieved by reducing anti-parkinsonian medications.
Another type of cell therapy involves stem cells. Some stem cells derived from embryos can develop into any kind of cell in the body, while others, called progenitor cells, are less flexible. Researchers are developing methods to improve the number of dopamine-producing cells that can be grown from embryonic stem cells in culture. Other researchers are also exploring whether stem cells from adult brains might be useful in treating Parkinson's disease.
Recent studies suggest that some adult cells from skin can be reprogrammed to an embryonic-like state, resulting in induced pluripotent stem cells (iPSC) that may someday be used for treatment of Parkinson’s. In addition, development and characterization of cells from people with sporadic or inherited Parkinson’s may reveal information about cellular mechanisms of disease and identify targets for drug development.
A number of early clinical trials are now underway to test whether gene therapy can improve Parkinson's disease. Genes which are found to improve cellular function in models of Parkinson's are inserted into modified viruses. The genetically engineered viruses are then injected into the brains of people with Parkinson's disease. Clinical studies have focused on the therapeutic potential of neurotrophic factors, including GDNF and neurturin, and enzymes that produce dopamine. These trials will test whether the viruses, by lending to the production of the protective gene product, improve symptoms of Parkinson's over time.
The National Institute of Neurological Disorders and Stroke also supports the Morris K. Udall Centers of Excellence for Parkinson's Disease Research program . These Centers, located across the USA, study cellular mechanisms underlying Parkinson’s disease, identify and characterize disease-associated genes, and discover and develop potential therapeutic targets. The Centers' multidisciplinary research environment allows scientists to take advantage of new discoveries in the basic, translational and clinical sciences that could lead to clinical advances for Parkinson’s disease.