Stem cell transplantation appears to produce mixed results as a treatment for Parkinson's Disease and further research is warranted, Columbia researchers have concluded, based on the most systematic study to date on the therapy's effectiveness.
The study, by Columbia and University of Colorado researchers, showed that stem cell surgery – an experimental type of treatment widely thought to hold great promise for treating many brain disorders – doesn't have immediate applications. However, experts say stem cell research should continue.
"It's not the answer to Parkinson's Disease, that's one thing," said Stanley Fahn, professor of neurology at Columbia's College of Physicians and Surgeons. But, he added, the study did provide "proof of principle" that the theories underlying the treatment are fundamentally sound.
Several experimental procedures involving stem cells are under research to treat brain disorders. Stem cells transplanted into the living brain develop into fully functioning neurons, or brain cells, thus replacing the brain's lost natural supply of cells. This may provide a more consistent and reliable solution to the disorder than drugs.
"Stem cell research should definitely go on, but it's not ready yet for humans," Fahn said. "People see this as a future savior, and it may be, but much more basic research is needed."
The study, published in the March 8 edition of the New England Journal of Medicine, found that the surgery brings limited benefits to Parkinson's patients aged 60 or younger. Older patients may not benefit.
Stem cells were implanted into the putamen, a brain region whose own cells degenerate in Parkinson's. The transplanted cells multiply and replace the brain's lost production of a needed neurotransmitter, or chemical messenger, called dopamine.
In the research, doctors monitored 40 patients to assess the outcomes of the surgery.
This was the first trial for this treatment to meet the "gold standard" of medical reliability, in that it followed a placebo-controlled, double-blind protocol. This means that about half the patients, as a control group, received a sham surgery in which surgeons did nothing more than drill a hole in the skull and that for a year after surgery, neither patients nor the researchers knew who had gotten the real surgery and who had received the false surgery.
After the surgery, the researchers conducted a variety of tests to assess patients' progress. Patients also evaluated their own conditions as a key part of the assessment process.
Columbia researchers recruited the test subjects, conducted their evaluations and responded to any complications or side effects. A Columbia statistician decided which patients would receive which operations.
"We got proof of principle that certain symptoms of Parkinson's Disease can improve" with the surgery, Fahn said.
"The statistical improvement occurred in the younger population, not the older group. And the major symptoms that got better were the symptoms of stiffness, and bradykinesia." Bradykinesia is a slowness of movement that hampers many basic daily activities of Parkinson's patients. However, other Parkinson's symptoms - such as tremors -- didn't improve, Fahn added.
Patients were asked to rate their own progress on a scale of between -3 and +3, depending on whether they had become worse or improved, respectively. One year after surgery, patients aged 60 or younger who had received the surgery rated themselves an average of +0.5, whereas patients in the same age group who had gotten the sham surgery rated themselves an average of -0.3.
Brain scans later showed that the transplanted cells functioned and multiplied as theorized in the patients' brains.
However, some of the transplant patients eventually developed a side effect of abnormal movements, which appeared to reflect an overproduction of dopamine, said Fahn. Probably, the transplanted cells "were working too much," he explained, and researchers must find a way to fine-tune their dopamine production.
"Until we can figure out the regulation of this, we at Columbia are not convinced that this is a procedure that should be utilized by everybody as a treatment right now," Fahn said. On the more hopeful note, he added, the patients are still being monitored, and it is possible that some older patients may see some delayed benefits of the surgery later on.
He added that stem cell surgery may still turn out to be the only hope for Alzheimer's disease, in which the transplanted cells may need to perform more complex functions that drugs cannot replicate. In Alzheimer's, the transplanted cells may be required to produce not only dopamine but trophic factors, which keep brain tissue alive.
The research was the first to receive a National Institutes of Health grant to study embryonic tissue transplants after a federal ban on funding fetal tissue research was lifted in January 1993.
--Office of External Relations, Columbia University Health Sciences Division, firstname.lastname@example.org.