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BACKGROUND. Recombinant human PDGF-BB (rhPDGF-BB) reduces Parkinsonian symptoms and increases dopamine transporter (DAT) binding in several animal models of Parkinson's disease (PD). Effects of rhPDGF-BB are the result of proliferation of ventricular wall progenitor cells and reversed by blocking mitosis. Based on these restorative effects, we assessed the safety and tolerability of intracerebroventricular (i.c.v.) rhPDGF-BB administration in individuals with PD. METHODS. We conducted a double-blind, randomized, placebo-controlled phase I/IIa study at two clinical centers in Sweden. Twelve patients with moderate PD received rhPDGF-BB via an implanted drug infusion pump and an investigation i.c.v. catheter. Patients were assigned to a dose cohort (0.2, 1.5, or 5 µg rhPDGF-BB per day) and then randomized to active treatment or placebo (3:1) for a 12-day treatment period. The primary objective was to assess safety and tolerability of i.c.v.-delivered rhPDGF-BB. Secondary outcome assessments included several clinical rating scales and changes in DAT binding. The follow-up period was 85 days. RESULTS. All patients completed the study. There were no unresolved adverse events. Serious adverse events occurred in three patients; however, these were unrelated to rhPDGF-BB administration. Secondary outcome parameters did not show dose-dependent changes in clinical rating scales, but there was a positive effect on DAT binding in the right putamen. CONCLUSION. At all doses tested, i.c.v. administration of rhPDGF-BB was well tolerated. Results support further clinical development of rhPDGF-BB for patients with PD. TRIAL REGISTRATION. Clinical Trials.gov NCT00866502. FUNDING. Newron Sweden AB (former NeuroNova AB) and Swedish Governmental Agency for Innovation Systems (VINNOVA)., Introduction Parkinson's disease (PD) is the second most common neurodegenerativo disease, affecting more than 5 million people worldwide. It is characterized by bradykinesia, rigidity, tremor, and gait disturbances, due to [...]

Transplantation of fetal brain tissue may be an effective treatment for patients with Parkinson's disease caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP-induced Parkinson's disease is a disorder caused by an injury to the brain cells that produce dopamine. Two immunosuppressed patients with severe MPTP-induced Parkinson's disease underwent transplantation with fetal brain tissue containing dopamine cells on both sides of their brain. Both of the patients experienced significant improvement in their motor skills and their ability to carry out daily activities after transplantation. One patient was able to decrease the dose of anti-Parkinson's medication received each day by 70%. The uptake of fluorodopa by either side of the brain was almost twice as high in both patients 12 to 13 months and 22 to 24 months after transplantation than before transplantation.

Abstract Background Balance impairment is one of the most distressing symptoms in Parkinson's disease (PD) even with pharmacological treatment (levodopa). A complementary treatment is high frequency stimulation in the subthalamic nucleus (STN). Whether STN stimulation improves postural control is under debate. The aim of this study was to explore the effects of STN stimulation alone on balance performance as assessed with clinical performance tests, subjective ratings of fear of falling and posturography. Methods Ten patients (median age 66, range 59–69 years) with bilateral STN stimulation for a minimum of one year, had their anti-PD medications withdrawn overnight. Assessments were done both with the STN stimulation turned OFF and ON (start randomized). In both test conditions, the following were assessed: motor symptoms (descriptive purposes), clinical performance tests, fear of falling ratings, and posturography with and without vibratory proprioceptive disturbance. Results STN stimulation alone significantly (p = 0.002) increased the scores of the Berg balance scale, and the median increase was 6 points. The results of all timed performance tests, except for sharpened Romberg, were significantly (p ≤ 0.016) improved. The patients rated their fear of falling as less severe, and the total score of the Falls-Efficacy Scale(S) increased (p = 0.002) in median with 54 points. All patients completed posturography when the STN stimulation was turned ON, but three patients were unable to do so when it was turned OFF. The seven patients with complete data showed no statistical significant difference (p values ≥ 0.109) in torque variance values when comparing the two test situations. This applied both during quiet stance and during the periods with vibratory stimulation, and it was irrespective of visual input and sway direction. Conclusion In this sample, STN stimulation alone significantly improved the results of the clinical performance tests that mimic activities in daily living. This improvement was further supported by the patients' ratings of fear of falling, which were less severe with the STN stimulation turned ON. Posturography could not be performed by three out of the ten patients when the stimulation was turned OFF. The posturography results of the seven patients with complete data showed no significant differences due to STN stimulation.

Parkinson's disease is a central nervous system disorder that involves a loss of neurons, or nerve cells, from the brain stem. Fetal neuronal tissue was used to try to counteract the loss of dopamine neurons in two patients with advanced Parkinson's disease. As is often the case, the patients responded to the commonly prescribed levodopa, but the drug was incompletely effective in controlling the symptoms of Parkinson's, and the patients were rigid and suffered loss of mobility. The grafting experiment required that the patients not be demented, as neurophysiological techniques would be used to detect changes that could not be observed clinically. Fetal tissue containing dopamine neurons was grafted into an area of gray matter of the brain, the caudate nucleus and putamen, using a stereotaxic apparatus and guidance from CT scanning. Positron emission tomography (PET) scan was used to identify the uptake of radioactively-labelled fluorodopa, which would indicate the presence of dopaminergic neurons. No changes were seen after five or six months, indicating that the number of surviving neurons must be small. Some changes in motor readiness suggested slowly improving function in the basal ganglia, but the persistence of symptoms did not indicate a reduced need for levodopa or bromocriptine. The technique of implanting fetal tissues into the brains of Parkinson's disease patients is worthy of further examination, but cannot yet be considered a therapeutic procedure. (Consumer Summary produced by Reliance Medical Information, Inc.)

Clinical trials using cells derived from embryonic ventral mesencephalon have shown that transplanted dopaminergic neurons can survive and function in the long term, as demonstrated by in vivo brain imaging using 18F-fluorodopa and 11C-raclopride positron emission tomography. Here we report the postmortem analysis of a patient with Parkinson's disease who 24 y earlier underwent unilateral transplantation of embryonic dopaminergic neurons in the putamen and subsequently exhibited major motor improvement and recovery of striatal dopaminergic function. Histopathological analysis showed that a dense, near-normal graft-derived dopaminergic reinnervation of the putamen can be maintained for a quarter of a century despite severe host brain pathology and with no evidence of immune response. In addition, ubiquitin- and α-synuclein-positive inclusionswere seen, some with the appearance of typical Lewy bodies, in 11-12% of the grafted dopaminergic neurons, reflecting the spread of pathology from the host brain to the transplants. Because the clinical benefits induced by transplantation in this patient were gradually lost after 14 y posttransplantation, our findings provide the first reported evidence, to our knowledge, that even a viable dopaminergic graft giving rise to extensive striatal reinnervation may lose its efficacy if widespread degenerative changes develop in the host brain. [ABSTRACT FROM AUTHOR]