Parkinson’s Disease: The Latest Research

By Kaaren Valenta

Researchers do not know what causes most Parkinson’s disease, and they have not found a cure, but a recent discovery involving a rare familial form of the disease gives hope to the 1.2 million people in the United States and Canada who have the slowly progressive disease of the nervous system.

Scientists investigating the rare type of early-onset Parkinson’s disease in an extended family in Iowa have discovered that an abnormal multiplication of the alpha-synuclein gene may cause that disease. The findings were the product of collaboration among scientists at several institutions, including researchers at the National Institutes of Health (NIH), part of the US Department of Health and Human Services.

The study provides major new clues into the process by which Parkinson’s disease develops. Further, it suggests another way of looking at the consequences of abnormal protein deposition in a variety of neurological diseases, such as Alzheimer’s disease.

Rowena E. Tabamo, MD, the associate director for clinical research at the Institute of Neurodegenerative Disorders in New Haven, keeps tabs on Parkinson’s research around the world. The institute is dedicated to research into Parkinson’s and other degenerative disorders.

“Parkinson’s is similar to Alzheimer’s disease in that it affects brain function,” Dr Tabamo told an audience at the November Lunch & Learn program sponsored by Ashlar of Newtown.

“We don’t know what causes Parkinson’s disease,” she said. “Certain genes can cause it, but most older persons with Parkinson’s disease don’t have those genes.”

Dr Tabamo said the brains of persons with Parkinson’s disease show a loss of darkly pigmented dopamine-producing cells in an area near the brain stem. “Usually there is a 30 to 50 percent dopamine cell loss for the symptoms of the disease to manifest themselves,” she said.

Parkinson’s disease is characterized by such symptoms Bradykinesia, which is a slowness or difficulty in initiating movement. Bradykinesia is the most prominent and disabling symptom of Parkinson’s.

The symptoms also can include rigidity or stiffness of the limbs, tremor when the body is at rest, a “mask face” that shows no expression, a shuffling gait, “freezing,” difficulty swallowing, changes in handwriting, and a flexed posture that causes instability.

The symptoms first described by British doctor James Parkinson in 1817 strike one person in every 100 over the age of 60. Many people with Parkinson’s disease, like actor Michael J. Foxx, show symptoms before the age of 40. Others, such as Pope John Paul II, developed the symptoms at later stages of their lives.

Today Parkinson’s disease is being assailed on several fronts. The speed at which it ravages the nervous system can be slowed, and scientists are confidently inching their way toward a cure.

“The research challenges are to understand how the cells die,” Dr Tabamo said. “Researchers are looking at genetic causes and the environment. It is likely it will be a combination of genetics and a predisposition plus environmental factors.

“It is important to diagnose the disease early,” she said, “but there is no definitive test, no blood test. It is more like a clinical diagnosis because an MRI or a CT scan will not show Parkinson’s disease. These tests are used only to rule out other possible causes.”

Dr Tabamo said risk factors for developing Parkinson’s disease include age (over 60), genetic/family history, exposure to chemicals such as pesticides and heavy metals, and repeated head trauma such as that experienced by former boxer Muhammad Ali.

Introduced in the 1960s, levodopa (also called L-dopa) is the most effective drug for controlling the symptoms of Parkinson’s. Levodopa is converted into dopamine in the brain, replacing the missing chemical and relieving the symptoms. Usually levodopa is given combined with carbidopa, a combination (Sinemet) that prevents or delays some of the side effects that often accompany levodopa therapy. Carbidopa also reduces the amount of levodopa needed by about 75 percent.

Levodopa is so effective that some people may almost forget they have Parkinson’s disease. But levodopa is not a cure. Although it can diminish the symptoms, it does not replace lost nerve cells and is does not stop the progression of the disease.

Over time, larger doses are needed to control the symptoms.

“In long-term use, the drug loses its effectiveness at higher doses,” Dr Tabamo said. “By six years many patients develop dyskenesia [abnormal involuntary movements].”

The drug also has possible side effects including nausea and vomiting, sleep disturbances, sweating, hallucinations, and light-headedness.

Dr Tabamo said there are several clinical studies of other drugs underway, but these are just the first step of a long drug-approval process. These studies are being conducted by drug companies, the National Institute of health, the Department of Defense, and through some institutional and individual grants.

Much of the work is very promising, she said.

“It’s exciting. There are studies on JNK [jun N-terminal kinase] inhibitors which seem to help prevent cell death, and neuroimmunophilin agents that may help cells grow back,” she said.

“If any of these are successful, they could be applied to many other diseases such as ALS or Alzheimer’s disease,” she said.