Study: Rogue Cells Explain Parkinson's Transplant Problem

Scientists working with Parkinson's disease patients who had pioneering transplant surgery using aborted fetal tissue have figured out what causes one of the most damaging side-effects of the treatment.

The finding opens the way for a revival of the controversial and unpredictable procedure, which was halted in the mid-1990s after many patients suffered bouts of serious sudden and uncontrolled movements.

Researchers from Britain and Sweden have found that the sudden movements, called dyskinesias, which are a common side effect of treatment for Parkinson's disease, are a result of excess serotonin cells in the transplanted tissue that trick the brain into releasing unregulated levels of dopamine.

Dopamine is a brain chemical that helps control movement, while serotonin is brain chemical which acts as a messenger.

Marios Politis of Imperial College London, who led the study, said its findings should allow scientists to modify the tissue used in future brain transplant trials for Parkinson's patients using fetal cells and from other sources, such as bioengineered cells or stem cells.

Politis and colleagues, whose results were published in the journal Science Translational Medicine on Wednesday, studied two Parkinson's patients who had received transplants of brain cells from aborted fetuses 13 and 16 years ago.

Although these patients experienced remarkable improvement in their Parkinson's symptoms and their transplants were still functional, they were suffering from troublesome dyskinesias.

Using positron emission tomography (PET) scans and radiotracers that can visualize the function of brain chemicals in living humans, the researchers found that the transplants had replaced some of the dopamine-producing brain cells that decay during Parkinson's disease.

But they also found abnormally high levels of serotonin-producing neurons within the transplanted tissue.

"The serotonin cells were very very highly excessive compared to what normal people have," Politis said in a telephone interview. "This provoked a false action by taking the dopamine and releasing it in an unregulated manner, and this created these involuntary movements."

Parkinson's is a neurodegenerative disease that affects one to two percent of people over the age of 65. Sufferers have tremors, sluggish movement, muscle stiffness, and difficulty with balance. Although drugs can improve symptoms for a while, there are none that can slow or halt the disease.

These study results come just ahead of a scheduled new round of experimental work due to be carried out by European and American experts, who plan to begin new brain tissue transplant trials in Parkinson's patients from 2012.

Politis said the study also suggested that drugs known as serotonin receptor agonists — such as the anxiety drug buspirone which is available as a generic and sold by Bristol-Myers Squibb under the brand Buspar — could be used to reduce dyskinesias in Parkinson's patients who are still suffering the side-effects from previous transplants.

But he said since buspirone was a short-acting drug, it would be good to see drug firms developing longer acting and slow-release versions which may be of more benefit.