Treatment

At present, there is no cure for Parkinson's Disease (PD). But medications or surgery can sometimes provide dramatic relief from the symptoms. Researchers are also exploring other approaches to treating PD, such as gene therapy and stem cells.

Medications

Medications for PD fall into three categories. The first category includes drugs that work directly or indirectly to increase the level of dopamine in the brain. The most common drugs for PD are dopamine precursors - substances such as levodopa that cross the blood-brain barrier and are then changed into dopamine. Other drugs mimic dopamine or prevent or slow its breakdown.

The second category of PD drugs affects other neurotransmitters in the body in order to ease some of the symptoms of the disease. For example, anticholinergic drugs interfere with production or uptake of the neurotransmitter acetylcholine. These drugs help to reduce tremors and muscle stiffness, which can result from having more acetylcholine than dopamine.

The third category of drugs prescribed for PD includes medications that help control the non-motor symptoms of the disease, that is, the symptoms that don't affect movement. For example, people with PD-related depression may be prescribed antidepressants.

Surgery

Treating PD with surgery was once a common practice. But after the discovery of levodopa, surgery was restricted to only a few cases. Studies in the past few decades have led to great improvements in surgical techniques, and surgery is again being used in people with advanced PD for whom drug therapy is no longer sufficient.

Pallidotomy and Thalamotomy. In pallidotomy, a surgeon selectively destroys a portion of the brain called the globus pallidus. It can improve symptoms of tremor, rigidity, and bradykinesia, possibly by interrupting the connections between the globus pallidus and the striatum or thalamus. A related procedure, called thalamotomy, involves surgically destroying part of the brain's thalamus. It is useful primarily to reduce tremor.

Because these procedures cause permanent destruction of brain tissue, they have largely been replaced by deep brain stimulation for treatment of PD.

Deep Brain Stimulation. It uses an electrode surgically implanted into part of the brain. The electrodes are connected by a wire under the skin to a small electrical device called a pulse generator that is implanted in the chest beneath the collarbone. The pulse generator and electrodes painlessly stimulate the brain in a way that helps to stop many of the symptoms of PD.

Treatments Under Development

Gene Therapy

Gene therapy is a technique that inserts genes into cells to produce specific proteins. A study of gene therapy in non-human primate models of PD is testing different genes and gene-delivery techniques in an effort to refine this kind of treatment. An early-phase clinical study is also testing whether using the adeno-associated virus type 2 (AAV2) to deliver the gene for a nerve growth factor called neurturin is safe for use in people with PD. Another study is testing the safety of gene therapy using AAV to deliver a gene for human aromatic L-amino acid decarboxylase, an enzyme that helps convert levodopa to dopamine in the brain. Other investigators are testing whether gene therapy to increase the amount of glutamic acid decarboxylase, which helps produce an inhibitory neurotransmitter called GABA, might reduce the overactivity of neurons in the brain that results from lack of dopamine.

Cell Therapy

Another approach to treating PD is to implant cells to replace those lost in the disease. Researchers are conducting clinical trials of a cell therapy in which human retinal epithelial cells attached to microscopic gelatin beads are implanted into the brains of people with advanced PD. The retinal epithelial cells produce levodopa. The investigators hope that this therapy will enhance brain levels of dopamine.

Starting in the 1990s, researchers conducted a controlled clinical trial of fetal tissue implants in people with PD. They attempted to replace lost dopamine-producing neurons 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. Unfortunately, some of the people who received the transplants developed disabling dyskinesias that could not be relieved by reducing antiparkinsonian medications.

Stem Cells

Another type of cell therapy involves stem cells. Stem cells derived from embryos can develop into any kind of cell in the body, while others, called progenitor cells, are more restricted. One study transplanted neural progenitor cells derived from human embryonic stem cells into a rat model of PD. The cells appeared to trigger improvement on several behavioral tests, although relatively few of the transplanted cells became dopamine-producing neurons. Other researchers are developing methods to improve the number of dopamine-producing cells that can be grown from embryonic stem cells in culture.

Researchers also are exploring whether stem cells from adult brains might be useful in treating PD. They have shown that the brain's white matter contains multipotent progenitor cells that can multiply and form all the major cell types of the brain, including neurons.

Reference:

National Institute of Neurological Disorders and Stroke, USA.