MDS Advises PD Patients to Stick to Stem Cell Trials

Pauline Anderson

August 22, 2013

Neurologists should advise patients with Parkinson's disease (PD) against seeking treatment with unproven stem cell therapies and only consider participating in cell therapy studies that are part of a research program affiliated with a recognized academic institution, a position paper from the Movement Disorder Society (MDS) advises.

The society fully supports research into the area of cell-based therapies, but such treatments are not yet proven to be of benefit and have not been published in recognized scientific journals that objectively scrutinize the procedures involved, the MDS statement said.

"Stem cells have achieved this almost mythical stature among patients with chronic disease who feel this might be the 'cure all,' " Matthew Stern, MD, Parker Family Professor of Neurology, University of Pennsylvania, Philadelphia, and president, MDS, told Medscape Medical News.

"As a result, there are a number of businesses that have been established, for better or worse, that offer stem cell therapies administered in a variety of ways. There is no evidence that whatever these particular organizations are providing really has any long-term benefits, and there may be some harm involved."

Treatments offered by these enterprises variously involve injections of stem cells into veins, spinal fluid, and even the brain.

"We have a ways to go," said Dr. Stern. "There's a lot of basic and clinical research that needs to be done before stem cell therapies are ready for prime time."

The MDS commissioned a brief review of the current place of cell-based therapies for PD. Its statement describes the different types of stem cells that are being explored, including their treatment potential and pitfalls. The MDS position paper was authored by a team led by Carolyn M. Sue, MBBS, PhD, FRACP, from the Department of Neurogenetics, Kolling Institute of Medical Research, Royal North Shore Hospital, University of Sydney, Australia.

Unbiased View

"This is our attempt at giving an unbiased view of the current state of the science to let people know what kind of advances have been made and where things need to go," said Dr. Stern.

One approach is to use a source of dopaminergic neurons to replace the function of those cells lost during the neurodegenerative process. Despite some advances, several challenges to using this type of cellular therapy remain.

"Improvements in the supply of cells that can survive and differentiate into true nigral dopaminergic neurons and effectively re-innervate the dopamine deficient areas of the [central nervous system] are still required," said the position paper

Even if successful replacement of dopaminergic neurons were viable, such a practice would not represent a "cure," as it would not address the treatment of dopamine-resistant motor features such as freezing and postural instability or the other no-motor features of the disease.

"The problem," said Dr. Stern, "is that PD is not really caused exclusively by loss of dopamine. The pathology is much more widespread and involves other systems. So you're not doing anything with dopaminergic stem cells other than replacing dopamine, and while that might be better than mediations, it's not going to cure the disease. It's not going to prevent other problems, the nondopaminergic problems like dementia, that can be much more disabling. The stem cells as they're being developed today are not designed to fix those more severe problems."

A more promising approach, said Dr. Stern, is to use neurotrophic stem cells that have an effect that goes beyond the dopamine system. According to other sources, this approach has in the past principally involved glial cell line–derived neurotrophic factor, which has produced mixed clinical effects.

A perhaps more practical method, although not necessarily the most effective according to Dr. Stern, might be to use stem cells that are derived from an individual, converted into dopaminergic neurons, and then used for autologous transplantation. This approach is based on the discovery that adult cells can be programmed to "rediscover" their regenerative properties. The technology here, however, is still being studied.

Another line of attack being pursued involves transplanting bone marrow–derived stromal cells and mesenchymal stem cells differentiated into dopaminergic neurons. Improved motor function has been reported in animal models with no evidence of tumor formation, but whether these cells are truly nigral dopaminergic neurons remains unproven.

In the area of neural stem cells (NSCs), some clinical studies have used human NSCs isolated from cortical-subcortical brain tissues, but these reports are "best regarded as being premature given that the scientific rationale underpinning them is poor," the statement notes.

No Outcome Info

The MDS stresses that there is no detailed scientific information available on the outcome of stem cell therapies now offered by organizations around the world. A recent case series that collected information retrospectively on 17 patients with parkinsonism who underwent intrathecal application of autologous unsorted bone marrow cells found there were no changes in motor function, activities of daily living, global clinical impression, or antiparkinsonian medication after a median observation period of 10 months. In this series, 2 patients reported worsening of PD symptoms, but the intervention was otherwise safe and well-tolerated.

"Intrathecal application of autologous bone marrow cells in such uncontrolled conditions did not produce clinical benefit in these patients," notes the statement.

According to the MDS, to provide good functional recovery to patients with PD, stem cell–based therapies need to show that:

  • "the cells can differentiate into authentic NIGRAL dopaminergic neurons;

  • they can survive and re-innervate the striatum;

  • release dopamine in response to physiological stimuli;

  • have functional benefits."

Therapies should produce no adverse effects such as immune reactions, tumor formation, or graft-induced dyskinesias. The latter are impossible to properly model in the laboratory, which makes the translation of such cells to the clinic not straightforward, said the statement.

"The future of cell-based therapies for PD requires an international approach through properly funded research and trials that should evolve in an iterative manner," said the statement. "At the moment the new trial being undertaken using fetal ventral mesencephalic tissue for PD in Europe may well represent the stepping-stone to future stem cell trials for PD."

The authors have disclosed no relevant financial relationships.

"MDS Position Paper: Use of Stem Cell Therapies for Parkinson's Disease." Full text

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