A new study by scientists in the US suggests that grafting fetal cells into a diseased brain as a way to treat Parkinson’s may not be effective in the long term because the disease is an ongoing process that eventually affects the new cells. The finding raises questions about the long term value of stem cell therapy in the treatment of Parkinson’s.
The study is the work of investigators at the Rush, Mount Sinai School of Medicine, New York, and the University of South Florida, Tampa, and is published in the April 6 issue of Nature Medicine.
Lead author and neuroscientist at Rush University Medical Center, Dr Jeffrey H Kordower, said they found evidence that fetal neuron cells grafted 14 years earlier into the brain of a woman who had Parkinson’s were affected in the same way that the disease affected the host dopamine neurons in the substantia nigra part of the woman’s brain.
The new cells had developed “Lewy body pathology”, the defining pathology for the disease, said Kordower, who is Jean Schweppe-Armour Professor of Neurological Sciences, professor of Neurosurgery, director of the Research Center on Brain Repair, and head of the section on Neuroscience at Rush.
The Lewy body pathology was confirmed using a staining method that showed evidence of alpha-synuclein and ubiquitin, and reduction of dopamine transporter.
“These findings give us a bit of pause for the value of cell replacement strategy for Parkinson’s disease,” added Kordower.
“We still need to vigorously investigate this approach among the full armament of surgically-delivered Parkinson’s disease therapies. While it is not clear to us whether the same fate would befall stem cell grafts, the next generation of cell replacement procedures, this study does suggest that grafted cells can be affected by the disease process,” he explained.
The woman described in the article had a 22 year history of Parkinson’s disease and was one of a group of patients who received fetal cell grafts in 1993 to reverse the loss of striatal dopamine in the brain.
After receiving the cell grafts, the woman’s symptoms improved, as measured by the Unified Parkinson Disease Rating Scale (UPDRS), and the fact her need for Parkinson’s related medication reduced significantly.
Her UPDS improvement held until 1997, but by 2004, said the investigators, her symptoms became progressively worse, and she died in 2007.
The investigators were able to study the brain of the deceased woman and also those of two other patients in her group who had received cell grafts at the same time.
The woman had the longest survival after transplant of all the patients in her group.
The investigators said that post mortem studies on patients that had not lived as long had shown a “robust survival of grafted neurons”, suggesting they were not affected by Parkinson’s.
But as Kordower explained, those individuals had not lived as long:
“Because Parkinson’s disease pathology progresses over decades, we think that the individuals did not live long enough for the Parkinson’s disease pathology to develop in the grafted cells.”
Scientists have speculated for some time about whether Parkinson’s is an ongoing pathological process that goes on to affect healthy cells, or whether it starts as a sudden event affecting only a certain number of cells.
Kordower and colleagues suggest their findings support the idea that the degenerative process is still there many years later, and is capable of affecting transplanted cells. And the process may destroy dopamine cells outside of the midbrain, they said.
Kordower said the findings also show that there may be:
“Either a pathogenic factor in the brain that affects dopamine producing neurons or a pathological process that can spread from one cellular system to another.”
“These findings have striking implications for understanding what causes [Parkinson’s Disease] and the potential for cell replacement strategies to reverse the motor symptoms,” he added.
Parkinson’s Disease usually strikes people over 50 and is a motor symptom disorder that results from the loss of brain cells that produce dopamine, which helps to smooth motor movement.
The four main symptoms are trembling hands, feet, legs, jaw and face, rigidity or stiffness of the limbs and trunk, slowing down of movement, and difficulty with balance and co-ordination. These eventually lead to difficulties speaking, walking, and doing simple every day tasks. Depression and emotional problems often accompany these more advanced symptoms.
The disease is difficult to diagnose and there is currently no cure although drugs that slow down the symptoms do exist.
According to the World Health Organization, in 1990 there were 4 million people worldwide living with Parkinson’s Disease.
“Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson’s disease.”
Jeffrey H Kordower, Yaping Chu, Robert A Hauser, Thomas B Freeman & C Warren Olanow.
Nature Medicine Published online: 06 April 2008.
DOI:10.1038/nm1747
Source: Rush University Medical Center press statement.
Written by: Catharine Paddock, PhD