Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New study in NEJM suggests levodopa may slow progression of Parkinson’s disease

10.12.2004


Levodopa is the most powerful drug available to treat the symptoms of Parkinson disease, and almost all patients with the disease will eventually need to take it. But there has long been controversy about when it should be started, in part because of concern that the medicine itself might cause further damage to the brain cells that are impaired in this disease. To resolve the controversy, a Columbia University scientist led a team of experts from the Parkinson Study Group to study levodopa’s effect on the rate of progression of the disease.



The study, reported in the December 9 issue of The New England Journal of Medicine, showed not only that levodopa does not appear to worsen the disease, but that it may actually slow its progression. A total of 38 Parkinson Study Group sites across the U.S. and Canada conducted this multi-center, placebo-controlled, double-blind clinical trial involving 361 newly diagnosed Parkinson disease patients.

Stanley Fahn, M.D., professor of neurology at Columbia University Medical Center, was the principal investigator of the study. “Although there is still uncertainty on how to interpret the study and further investigation will be necessary to prove levodopa’s value beyond reasonable doubt, we found that levodopa did not accelerate the pace of Parkinson disease,” said Dr. Fahn. “Now patients can feel more secure about the drug and may wish to start it sooner rather than later.”


The co-principal investigator, Ira Shoulson, M.D., professor of neurology at the University of Rochester, added, “The results of this study are important because they help provide confidence for both patients with Parkinson disease and their doctors about the safety of levodopa.” Drs. Fahn and Shoulson advised, however, “The results do not prove that levodopa slows the underlying nerve degeneration of Parkinson disease, and a differently designed clinical study will be necessary to address this concept.” A follow-up study is already in the planning stages. Drs. Fahn and Shoulson further cautioned, ”The high dose required for the best effect produced more undesirable side effects, such as abnormal involuntary movements, which is another reason patients have delayed starting levodopa.”

About Parkinson’s Disease

Parkinson’s disease is a progressive neurological disorder that affects approximately 1.5 million Americans. The disease is characterized by tremor, stiffness, slowness and eventually poor balance control. The symptoms are due to loss of nerve cells in the brain that contain “dopamine.” The most effective treatment for Parkinson’s is dopamine replacement therapy with the drug levodopa, which is changed to dopamine in the brain. Levodopa is commonly sold in combination with carbidopa under the brand name “Sinemet” or its generic equivalent. Over time, Parkinson disease continues to worsen, and new symptoms emerge that do not respond as favorably to levodopa therapy. Because Parkinson’s is a progressive disorder, the symptoms worsen with time.

About the Study

Research physicians at Columbia University Medical Center and 37 other Parkinson Study Group sites in the United States and Canada evaluated 361 newly diagnosed participants with early Parkinson disease. There were four treatment groups: (1) carbidopa/levodopa 12.5/50 mg three times daily; (2) carbidopa/levodopa 25/100 mg three times daily; (3) carbidopa/levodopa 50/200 mg three times daily; and (4) matching placebo. Neither the study participants nor the investigators were aware of the treatment assignments. After 40 weeks (9 months) of treatment, the medications were withdrawn, and 2 weeks later, after allowing the symptomatic benefit of levodopa to dissipate, the subjects were evaluated to see how far the disease had worsened since the baseline examination 42 weeks earlier. The placebo-treated group represented the natural progression of the illness.

The primary outcome of the study was to measure Parkinson impairment between the beginning of the study (week zero) and the end of the study (week 42). If levodopa accelerated disease progression, then those treated with levodopa would be expected to have more severe impairment than the placebo-treated group after the symptomatic benefit of levodopa had been eliminated through the 2-week washout phase. If levodopa slowed progression, then the levodopa-treated subjects would be expected to have less severe Parkinson disease than the placebo-treated group.

The clinical results showed a clear-cut benefit in favor of levodopa. Moreover, the higher the dosage, the more beneficial the result. A question remains, however, as to whether the 2-week washout of the drug was sufficient to account for the elimination of all of levodopa’s symptomatic benefit.

The study also contained a brain imaging component that showed the opposite effect from the clinical research evaluations. Participants underwent evaluation of their dopamine neurons at the beginning of the study and again after 40 weeks of treatment. These results suggest that levodopa could possibly have accelerated the loss of dopamine neurons. These findings also raise the question as to whether levodopa treatment interfered with the imaging by temporarily altering the chemistry of the dopamine neurons.

The PSG (www.Parkinson-Study-Group.org) is a non-profit, cooperative group of Parkinson disease experts from medical centers in the United States and Canada who are dedicated to improving treatment for persons affected by Parkinson disease.

The National Institutes of Health and the Department of Defense’s Neurotoxin Project provided financial support for this study, known as the ELLDOPA (Earlier versus Later LevoDOPA Therapy in Parkinson Disease) Study. Teva Pharmaceuticals Industries of Netanya, Israel, which markets generic levodopa, provided the supply of levodopa and matching placebos gratis.

Columbia University Medical Center provides international leadership in basic, pre-clinical and clinical research, medical education, and health care. The medical center trains future leaders in health care and includes the dedicated work of many physicians, scientists, nurses, dentists, and other health professionals at the College of Physicians & Surgeons, the School of Dental & Oral Surgery, the School of Nursing, the Mailman School of Public Health, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. With a strong history of some of the most important discoveries in health care, its researchers are leading the development of novel therapies and advances to address a wide range of health conditions.

Karen Zipern | EurekAlert!
Further information:
http://www.columbia.edu

More articles from Studies and Analyses:

nachricht The Great Unknown: Risk-Taking Behavior in Adolescents
19.01.2017 | Max-Planck-Institut für Bildungsforschung

nachricht A sudden drop in outdoor temperature increases the risk of respiratory infections
11.01.2017 | University of Gothenburg

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

New Study Will Help Find the Best Locations for Thermal Power Stations in Iceland

19.01.2017 | Earth Sciences

Not of Divided Mind

19.01.2017 | Life Sciences

Molecule flash mob

19.01.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>