Clinical Trials of Stroke Therapy

Abstract

Despite recent advances in stroke prevention and acute stroke therapy, few treatments exist for reversal of fixed neurological deficits after stroke. Cellular therapy offers the possibility of improving neurological deficits months or even years after stroke. Animal studies provide evidence that such treatment may be effective. Many questions, however, remain unanswered regarding cellular therapy for stroke. In view of the significant differences between animal models and human stroke, some questions might be best addressed with clinical trials. Completed clinical trials of cellular therapy for stroke are summarized in the Table. Kondziolka et al reported the results of a Phase I study of 12 patients with completed stroke involving the basal ganglia treated with human neuronal cells derived from an immortalized tumor cell line (LBS cells).1 Either 2 or 6 million cells were implanted stereotactically between 6 months and 6 years after stroke. Patients were followed clinically as well as with MRI and positron emission tomography scans. The same group subsequently performed a Phase II study with randomization of 18 patients to either implantation of 5 or 10 million cells and rehabilitation (14 patients) or rehabilitation alone (4 patients).2 Follow-up neurological evaluations were blinded to treatment status. Savitz et al reported the results of transplantation of fetal porcine cells implanted stereotactically in 5 patients with basal ganglia stroke 3 months to 10 years after onset.3 The study was discontinued due to adverse events in 2 patients. In a study by Bang et al, autologous mesenchymal stem cells were given intravenously to 5 patients with middle cerebral artery territory strokes 4 to 5 weeks and again at 7 to 9 weeks after onset.4 An additional 25 patients served as control subjects. All patients were followed for functional outcome and adverse events. View this table: Table. Clinical Trials of Cellular Therapy …