Parkinson's drug may slow disease

A drug currently used to treat the symptoms of Parkinson's Disease (PD) may actually slow the progression of the disease. In preliminary laboratory tests, UK researchers found that the dopamine agonist, pramipexole, may protect brain cells from dying.

Parkinson's Disease, which affects around 120,000 people in the UK alone, is caused by a progressive deterioration of the brain nerve cells that help control movement. It is often characterised by difficulty in walking, movement and coordination and most often develops after the age of 50. Only when around 50-80% of the dopamine producing nerve cells are lost do the symptoms become apparent.

There is no known cure for PD and current treatments aim to substitute the brain dopamines by various means to relieve the symptoms. Pramipexole, marketed under the name Mirapexin by Pharmacia, is currently used to treat patients of PD.

The study's author, neurologist Anthony Schapira of the Royal Free and University College Medical School, London, said, 'If additional studies can confirm that this drug can protect nerve cells, then I think the emphasis would shift to prescribing it as early as possible in the cause of the disease.'

The drug appeared capable of protecting the cells when they were exposed to toxins, the study found. 'The pramipexole significantly decreased the effects of the 1-methyl-4-phenylpyridinium (MPP+), which is known to induce PD, on cell death and on the mitochondria — generally by about 50%,' Schapira said. 'If the results can be duplicated in humans, it could significantly alter the way doctors treat PD. Early detection in PD would become critical and the potential benefits of early genetic screening would be apparent.'

At a recent Helsinki conference, a number of lectures and presentations reviewed preliminary scientific studies that have now paved the way for testing dopamine agonists as putative neuroprotective agents in PD. A number of biochemical abnormalities in the parkinsonian substantia nigra are thought to contribute to the pathogenesis of PD, such as mitochondrial complex I deficiency and free radical-mediated damage. Both processes may affect the mitochondrial membrane potential, a major determinant of mitochondrial mediated apoptosis. Several dopamine agonists have been shown to have free radical scavenging properties, and to offer some protection to cell lines against certain toxins including MPP+, the active metabolite of the neurotoxin MPTP which causes a parkinsonian-like syndrome in experimental models.

A poster presentation by Prof Anthony Schapira's team detailed results of study evaluations using human neuroblastoma dopaminergic SHSY5Y cells to investigate the potential mechanisms of protection offered by the dopamine D2 receptor agonist pramipexole. Pramipexole decreased the effects of the MPP+ iodide on cell death and on the mitochondria membrane potential in tumour cell culture. If these results can be confirmed, it would suggest that this drug may have a modifying effect on the progress of the disease. Schapira said additional studies are underway to see if the results can be confirmed.

The findings suggest that in tumour cell culture, daily treatment with Pramipexole maintains mitochondrial membrane potential and thus protects neuronal cells from apoptotic cell death induced by the parkinsonian neurotoxin, MPP+.