Stem cells for Parkinson's disease: advancing science but protecting patients.

In this issue of Movement Disorders, Storch et al. report on the results of 17 patients with a variety of parkinsonian disorders who received treatment with intrathecal bone-marrow–derived mesenchymal stem cells (BMCs) at ‘‘stem cell’’ clinics in Germany and Italy. The patients were self-referred and paid the clinics 6,000 to 30,000 Euros per procedure. None of the patients were found to have shown improvement on any measure of PD, including the H & Y scale, the Schwab and England (S & E) Scale, or UPDRS Part III and II—indeed, there was an overall trend to worsening. Fortunately, there were no clinically meaningful side effects. The authors themselves did not perform or recommend the procedures. Patients were ascertained based on a survey of members of the German Neurological Society and the German Parkinson Disease Society seeking patients who had undergone this procedure. All were evaluated by movement disorder specialists a mean of 8 months after undergoing transplantation. All but 3 patients had been examined before the procedure, and baseline information on the remainder was gained by retrospective chart review. Details of the procedure available to the investigators are sketchy. Apparently, autologous stem cells derived from bone marrow preparations (aBMC) standardized by their content of CD34þ hematopoietic stem cells were administered intrathecally (IT) and intravenously (IV). There was no indication that the procedure was approved by an institutional review board (IRB) or federal regulatory agency, or that the patients had given informed consent. There is no indication that the physicians who performed this procedure had scientific expertise or traning in this area, or had performed any preclinical studies in preparation for initiating treatment. Indeed, there is little or no scientific data demonstrating that BMCs administered IT or IV provide benefit in animal models of PD. Cognitive scores are not provided, but UPDRS and S & E scores indicate profound disability, and it is by no means clear that patients had the capacity to make an informed decision. Finally, there is no indication that the treating physicians performed follow-up evaluations or made any attempt to determine the safety and efficacy of the procedure or to disseminate this information to colleagues. Current therapies provide considerable benefit for PD patients. However, treatment is limited by the development of motor complications, other drug-related side effects, the emergence of nondopaminergic features that are not adequately controlled with available therapies such as falling, freezing, and dementia, and inexorable disease progression. Cell-based therapies, based on the concept of transplanting or delivering dopaminergic neurons into the striatum (and midbrain) to replace those that have undergone neurodegeneration, have attracted considerable attention as a possible means of overcoming some of these limitations. Implanted fetal mesencephalic dopamine (DA) neurons have been demonstrated to survive, reinnervate the striatum, release DA, and provide benefit in rodent and primate models of PD. In PD patients, transplanted mesencephalic grafts have been reported to provide clinical benefit in open-label studies, and postmortem studies have demonstrated robust survival of implanted embryonic DA neurons with organotypic innervation of the striatum. However, two shamcontrolled, double-blind, controlled trials failed to show significant clinical benefit, and patients in each study developed a previously undescribed form of graft-induced dyskinesia that persisted even after withdrawal of levodopa. Nevertheless, there are several reasons why cellbased strategies continue to remain a focus of interest among PD investigators. Subanalyses of patients who participated in the double-blind trials showed significant benefits in those who were younger and had milder disease with fewer nondopaminergic features at baseline. Long-term studies of patients in open-label -----------------------------------------------------------*Correspondence to: C. Warren Olanow, Department of Neurology and Neuroscience, Mount Sinai School of Medicine, New York, New York, USA; Warren.olanow@mssm.edu