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From the Departments of Neurology (Dr. Hauser and H. Delgado), Neurosurgery (Drs. Sanberg and Freeman, and D. Scott), Pharmacology and Experimental Therapeutics (Drs. Hauser, Sanberg, and Freeman), Medicine (Dr. Holt), Psychology (Dr. Cimino and E. Soety), the Neuroscience Program (Drs. Hauser, Sanberg, and Freeman), and College of Public Health (Dr. Schwartz), University of South Florida, Tampa; Tampa General Healthcare (Drs. Hauser, Eichler, and Freeman, and D. Scott); Women’s Center (Dr. Nauert), Tampa, FL; and Neurodegenerative Disorders Center (Drs. Furtado, Sossi, and Stoessl), University of British Columbia, Vancouver, Canada.
Address correspondence and reprint requests to Dr. Robert A. Hauser, Parkinson’s Disease and Movement Disorders Center, University of South Florida, 4 Columbia Drive, Suite 410, Tampa, FL 33606; e-mail: rhauser{at}hsc.usf.edu
Background: Transplanted striatal cells have been demonstrated to survive, grow, establish afferent and efferent connections, and improve behavioral signs in animal models of Huntington’s disease (HD).
Objective: To evaluate feasibility and safety and to provide preliminary information regarding the efficacy of bilateral human fetal striatal transplantation in HD.
Methods: Seven symptomatic patients with genetically confirmed HD underwent bilateral stereotactic transplantation of two to eight fetal striata per side in two staged procedures. Tissue was dissected from the lateral half of the lateral ventricular eminence of donors 8 to 9 weeks postconception. Subjects received cyclosporine for 6 months.
Results: Three subjects developed subdural hemorrhages (SDHs) and two required surgical drainage. One subject died 18 months after surgery from probable cardiac arrhythmia secondary to severe atherosclerotic cardiac disease. Autopsy demonstrated clearly demarcated grafts of typical developing striatal morphology, with host-derived dopaminergic fibers extending into the grafts and no evidence of immune rejection. Other adverse events were generally mild and transient. Mean Unified HD Rating Scale (UHDRS) motor scores were 32.9 ± 6.2 at baseline and 29.7 ± 7.5 12 months after surgery (p = 0.24). Post-hoc analysis, excluding one subject who experienced cognitive and motor deterioration after the development of symptomatic bilateral SDHs, found that UHDRS motor scores were 33.8 ± 6.2 at baseline and 27.5 ± 5.2 at 12 months (p = 0.03).
Conclusions: Transplantation of human fetal striatal cells is feasible and survival of transplanted cells was demonstrated. Patients with moderately advanced HD are at risk for SDH after transplantation surgery.
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