Mayo Clinic Health Letter: New treatments, still no cure

Volume 19, Number 3, May 2001—Reprinted with permission of Mayo Clinic

Tremors. Speech problems. Walking difficulties. Over half a million Americans live with the frustrating symptoms of Parkinson's disease.

Doctors and researchers continue to develop new drugs and new approaches to treating Parkinson's. These can help minimize disabling symptoms and help people live independently longer. However, the search for a cure continues.

A chemical loss

Parkinson's disease is a neurological disorder that causes gradual, progressive loss of control over movement. These movement problems are primarily caused by inadequate levels of dopamine, a chemical that transmits messages from an area of your brain called the substantia nigra to other parts of the brain that control muscles throughout your body.

People with Parkinson's have substantially less dopamine than normal. Symptoms typically become evident when dopamine is about 60 percent to 80 percent below normal.

Researchers still don't know what causes some people to produce less dopamine than normal. Age may play a role. Although symptoms may begin even before 40, most people with the condition begin to experience symptoms later in life. In addition, risk of Parkinson's increases with age.

Your risk of getting Parkinson's

Parkinson's disease experts at the Mayo Clinic have studied the incidence of the disease among different age groups. The table below lists the number of people, per 100,000 person years, in each age group who will likely acquire Parkinson's disease. The numbers don't include the people who acquired Parkinson's at a younger age and continue to live with it.

Sex / Age

40-49

50-59

60-69

70-79

80-89

All ages

Men

5 25 97 241 381 22

Women

1 11 50 114 178 16

Signs and symptoms

You may have Parkinson's disease for years before it seriously affects your life. In most people with Parkinson's, at least two of three signs and symptoms are present early in the disease:

  • Slowness of movement (bradykinesia) - Problems with moving quickly or smoothly often develop first. It may be difficult to plan and begin movements. Bradykinesia may affect all areas of daily life, from taking the first step out of a chair to signing your name.
  • Tremor - Tremor most often begins in one hand and resembles rolling a pill between your thumb and the tip of your forefinger. Tremor is most noticeable at rest and often disappears during purposeful movement or sleep. As tremor progresses, it may also affect your legs or jaw. However, about a third of people with Parkinson's have no tremor.
  • Rigidity - In early stages of Parkinson's, rigidity - experienced as a sense of stiffness - is most often noticeable when limbs resist being moved.

As the disease progresses, a number of other signs and symptoms can appear that further limit your ability to function:

  • Impaired posture and balance - it may become more difficult to sit or stand straight. Stooping or leaning forward, along with slowness and shuffling, leads to the characteristic walk of Parkinson's disease. Loss of balance can cause a feeling of falling, particularly forward. Poor balance may not be helped by Parkinson's medications.
  • Speech problems - An early sign of Parkinson's is often a loss of voice volume, speed and clarity.
  • Mood changes - Anxiety and depression are common.
  • Memory loss - As Parkinson's progresses, memory loss and other signs of dementia may develop. It's estimated that about a quarter of people with Parkinson's eventually develop dementia. Dementia often can't be helped with the common Parkinson's drug therapies. In fact, some medications commonly used to treat Parkinson's may actually make dementia worse.

Treatment options

Treating Parkinson's involves finding the right mix of medications for the particular stage of the disease. Not everyone responds the same way to the same medications, and it's likely that your treatment will change as the disease progresses. To start with, doctors may prescribe one of three types of drugs:

  • Dopamine replacer - Levodopa, a medication that's converted to dopamine in your brain, has been the most common drug used to treat Parkinson's. It was developed in the 1960's and has allowed many people to live independently longer than was previously possible.

    Levodopa is usually prescribed as a carbidopa-levodopa combination (Atamet, Sinemet), Carbidopa protects levodopa and prevents it from being metabolized before it's converted to dopamine in the brain. Carbidopa also reduces side effects, such as nausea and vomiting, sometimes associated with levodopa.

    Levodopa helps lessen Parkinson's symptoms, especially slowness of movement and rigidity. However, its effects may wear off between doses, and its effectiveness may lessen over time. This results in fluctuations among normal, smooth movement, slow movement with tremor and sometimes excessive movements called dyskinesia (dis-kih-NEE-zhuh).

    Changing the dosing schedule or adding other medications often alleviates these effects. In addition, a controlled-release carbidopa-levodopa medication often provides benefits that last longer.

  • Dopamine agonists - Dopamine agonists mimic the role of dopamine in the brain and can be used alone or in combination with levodopa. They are often used very early in treatment of the disease or later on, when levodopa's effects start to wear off. They aren't as potent as levodopa but have a longer-lasting effect.

    Drugs in this class include two older medications, bromocriptine (Parlodel) and pergolide (Permax), and two newer versions, pramipexole (Mirapex) and ropinirole (Requip). They are usually more expensive than levodopa and may cause side effects such as paranoia, hallucinations or drowsiness.

  • Dopamine extenders - These newer medications help to increase dopamine's action. They do so by blocking enzymes that can inactivate dopamine in the brain. Drugs of this class include selegiline (Alapryl, Carbes, Eldepryl), tolcapone (Tasmar) and entacapone (Comtan).

    Selegiline helps to delay the breakdown of dopamine by inhibiting the action of the enzyme type B monoamine oxidase (MAO-B). It's sometimes given by itself, before starting levodopa, but can also be given in combination with levodopa.

    Toxic reactions have occurred in some people who took selegiline with the narcotic pain reliever meperidine (Demerol).

    Tolcapone and entacapone increase dopamine's action by inhibiting the enzyme catechol O-methyl-trannsferase (COMT). They're taken in combination with levodopa. However, tolcapone has, rarely, caused liver failure and requires close monitoring of liver function while taking it. Entacapone has not caused these side effects.

Surgical options

In people whose symptoms can't be controlled by medications, doctors may consider surgery such as:

  • Deep brain stimulation - In this new procedure, a thin wire is implanted in the thalamus and connected to an electric stimulator similar to a heart pacemaker. While the stimulator is on, electrical impulses stop the tremor on one side of your body. This procedure may have an advantage because it doesn't destroy brain tissue.
  • Pallidotomy - This procedure has been used for over 50 years. A wire placed in an area deep within the brain, called the pallidum, destroys tissue when the tip of the wire is heated. The procedure tends to relieve tremor. It may also improve other aspects of Parkinson's.

Future treatments

Researchers are focusing on finding new ways to treat and possibly cure Parkinson's disease. One method being tested involves transplanting fetal nerve tissue to replace lost dopamine neurons in the brain. This has raised ethical questions and has shown mixed results in trials.

Another method involves inserting a gene into the affected region of the brain to replenish loss of dopamine and dopamine-producing cells. Both procedures are still unproven in treating humans.