DBS has been found to be effective for diseases other than PD. It also helps in patients with essential tremor, dystonia, and obsessive compulsive disorder too. Like PD, essential tremor causes rhythmic shaking in the limbs, head, or voice. Dystonia is characterized by involuntary muscle contractions, resulting in contorted movements or postures.

When it comes to medicinal therapies, the drug levodopa, first used in 1967, remains the primary drug of choice to combat symptoms, although today it is combined with other drugs to prevent uptake by the peripheral nervous system (the brain is part of the central nervous system) and slow its metabolic breakdown. Even so, in it most common form a mix of levodopa and carbidopa, it has a short half life— about 90 minutes. By itself, levodopa’s half life is only 45 minutes.

Doctors sometimes prescribe levodopa/carbidopa to aid in PD diagnosis. If the patient takes the drug and symptoms diminish, the diagnosis is PD. If not, it’s something else.

Since the advent of levodopa six drug classes have been developed to treat PD.

Dopaminergic drugs like levodopa mimic dopamine. Decarboxylase inhibitors such as carbidopa slow the breakdown of dopamine-like drugs. Dopamine agonists, for example mirapex, bind to dopamine receptors and imitate dopamine. Some clinicians argue that levodopa poses toxicity problems because its oxidative mechanism leads to increased generation of hydrogen peroxide. This in turn leads to more brain damage. They support use of dopamine agonists as an alternative.

Anticholinergics, e.g. benztropine, block the neurotransmitter acetylcholine and relax smooth muscle such as the bicep or triceps.

MAO inhibitors block a metabolic pathway that stops activity of monoamine oxidase. There are two types: MAO-A and MAO-B; dopamine is broken down by both. A drug that blocks MAO-B breakdown is azilect. Azilect may be the most important drug developed since levodopa because there is empirical evidence that it slows, if not reverses, PD. In an 18-month long, double blind study of 1,176 subjects, azilect, in 1 mg daily doses, was shown to slow the progression of PD. The study, called ADAGIO (Attenuation of Disease Progression with Azilect Given Once-daily) had an interesting result: daily 2 mg doses were less effective than the 1 mg doses. The different outcomes corresponding to the two different doses have yet to be explained, and some argue the improvement at a lower dosage is a false-positive result.

Azilect represents a breakthrough in another important way. Usually MAO inhibitors require strict drug and dietary restrictions. For example, cold remedies or foods such as soy bean products, air dried meats, and aged cheeses have to be avoided because they contain tyramine, an amino acid. Tyramine, when ingested by a person on an MAO inhibitor can cause a dangerous increase in blood pressure because it is not broken down. But azilect, in 1 mg or 0.5 mg doses, has been found to be selective in its action and does not stop tyramine breakdown, and thus is not subject to dietary restrictions.

Another metabolic pathway is called the COMT. The drug entacapone works to block this and is often combined with carbidopa and levodopa in a drug called stalevo. Often, two or three drugs are administered at the same time.

There are several disadvantages to drug therapy. One is that over time it generally becomes less effective. Essentially, the body builds up a tolerance for levodopa. A second problem is the cost. Medication typically costs $2,500 to almost $6,000 per year. While insurance sometimes reduces out of pocket expenses, overall cost remains high.

Regardless of their specific roles, i.e. delivering a signal or controlling a pump, electronic devices will play a critical role in the treatment of people with Parkinson’s disease.

The enigma of Parkinson’s

Despite almost 200 years of study, and 60,000 new patients a year, Parkinson’s Disease (PD) remains one of the most difficult diseases to diagnose and treat. It is difficult to diagnose because there are no readily measurable biomarkers: nothing to be measured in a patient’s blood or serum, and nothing readily visible in MRI scans or radiographs. Currently, available treatments only diminish symptoms. There is no cure for the disease itself and little evidence of one being on the horizon.

PD becomes apparent when 50 to 80% of the brains’ dopamine producing cells die off. Dopamine production occurs in several different brain structures, most notably in the substantia nigra, medulla, and the ventral tegmental area. The cause of the cell die-off remains a mystery, but there is a considerable amount of evidence pointing to a cellular inclusion called Lewy bodies. Lewy bodies are also present in Alzheimer’s and other central nervous system disorders. Why Lewy bodies develop is anyone’s guess. Three factors may be at work: genetics, environmental, and physical trauma. The general consensus is that genetics predispose a person to the condition, and the environment or trauma activates it.

However, questions remain even with this hypothesis. For example: What caused people to contract the disease 200 years ago, when modern day environmental stimuli were non-existent?

For more on PD . . .

Several organizations are available to provide help both for people with PD and for researchers. These include the Parkinson’s Disease Foundation and the Davis Phinney Foundation. Both of these organizations provide guidance and help for people with PD, as well as funding for PD research. PDF also leads PDtrials, a collaborative initiative of Parkinson’s organizations dedicated to increasing education and awareness about clinical research. Central to this effort is providing information to help people with Parkinson’s learn more and make informed decisions about participating in clinical studies. PD Trials offers a forum for phase1, phase 2 and phase 3 studies.