Medical Edge Newspaper Column

New Treatments for Parkinson's: Gold Standard Still Prevails

March 26, 2007
Dear Mayo Clinic:
What are some of the latest treatments for Parkinson's disease? -- Hyannis, Mass.

Answer:
The U.S. Food and Drug Administration approved a new drug for Parkinson's disease (PD) in May 2006 and positive results on a PD medication delivered via skin patch were announced in January 2007. Three other drugs were introduced over the past three years, too. But before describing these innovations, let me briefly describe what was already available.

Since its introduction in the 1960s, levodopa -- a substance found in plants and animals -- has been the gold-standard drug therapy for Parkinson's disease. Nerve cells in the brain convert levodopa into the neurotransmitter dopamine, and the resulting increase in dopamine concentration can temporarily reverse some of PD's disabling symptoms, which include tremor, rigidity, slowness of movement, and walking problems. Many Parkinson's disease symptoms are caused by damage to brain cells that naturally produce the body's dopamine.

Treatment with dopamine itself doesn't help because dopamine cannot cross the body's blood-brain barrier. Levodopa can cross the blood-brain barrier, and when combined with the drug carbidopa its peripheral breakdown is reduced, allowing even more levodopa to get into the brain. Carbidopa plus levodopa (Sinemet) typically enables people with PD to extend the time they are able to lead relatively normal lives -- often, for a good many years.

The innovations cited above offer variations on the carbidopa/levodopa theme rather than fresh approaches; i.e., they work through brain dopamine. The drug approved last May -- rasagiline (Azilect) -- is an inhibitor of monoamine oxidase B (MAO-B), an enzyme that metabolizes dopamine. It is very similar to selegiline, a drug that has been available for a number of years. Each of these medications may be administered either with carbidopa/levodopa or as sole therapy. They benefit PD symptoms, albeit not dramatically.

The new skin patch delivers a drug called rotigotine (Neupro), which is a dopamine "agonist." Dopamine agonists mimic dopamine's effects; i.e., they behave like synthetic forms of dopamine. Rotigotine and other dopamine agonists (e.g. ropinirole, pramipexole) are used both as adjuncts to carbidopa/levodopa therapy and also initially in early Parkinson's disease, especially in younger adults. The potency of the skin patch appears to be similar to the oral drugs already on the market.

The three other new drugs include Stalevo, Parcopa and injectable apomorphine. Stalevo is a combination of carbidopa/levodopa and entacapone (Comtan). The latter is an inhibitor of catechol-O-methyltransferase (COMT) -- another enzyme that breaks down dopamine. Parcopa is an alternate tablet form of carbidopa/levodopa that rapidly disintegrates in the mouth, dissolves in saliva, and is absorbed by the body when swallowed. It can be used when water or other fluids are not readily available, say, at some social event or work situation. Apomorphine (Apokyn) is a dopamine agonist that is injected for quick relief of parkinsonian states when the levodopa effect has unexpectedly worn off. It works quickly, usually in less than 10 minutes, with 60-90 minutes of relief.

All in all, though, the foundation of Parkinson's disease treatment is still carbidopa/levodopa. It is the most effective and least costly. For patients whose PD symptoms cannot be sufficiently managed with medications alone, a relatively new alternative is deep brain stimulation (DBS). A pacemaker-like unit implanted in the chest transmits electric impulses through a wire to tiny electrodes inserted into the brain's subthalamic nucleus, which is an integral component of the motor-control circuitry. This process reproduces the levodopa response.

Not all PD patients are DBS candidates, however. It doesn't work in patients who are completely unresponsive to levodopa, and it doesn't improve symptoms beyond those responsive to levodopa. It is an excellent treatment for patients with fluctuating levodopa responses or with excessive movements, known as dyskinesias, caused by medications.

Looking to the future, the most exciting avenue of research is the recognition that the protein alpha-synuclein is a major component of Lewy bodies -- abnormal clumps within nerve cells that are the pathological markers of Parkinson's disease. Genetic defects in the alpha-synuclein gene cause a rare inherited form of PD, suggesting that alpha-synuclein may be a central component in all PD and thus a target for new and better treatments.

-- J. Eric Ahlskog, M.D., Ph.D., Neurology, Mayo Clinic, Rochester, Minn.