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MRI volumetric and intensity analysis of the cerebellum in Parkinson's disease patients infused with glial-derived neurotrophic factor (GNDF) H Chebrolu, JT Slevin, DA Gash, GA Gerhardt, B Young, CA Given, CD Smith Experimental Neurology 2006;198:450-456 GDNF at therapeutic doses does not cause cerebellar changes in PD patients, according to this study. The risk of cerebellar pathology was one factor leading to the discontinuation of GDNF trials in 2004, as reported by E-MOVE and archived HERE. http://www.mdvu.org/emove/article.asp?ID=762 Nine patients who received GDNF in the Kentucky trial underwent brain MRI before infusion and after a mean of 15 months treatment. Pre- and post-treatment comparison revealed no significant changes in any patient cerebellum, nor any changes in the group as a whole. No hyperintensity on FLAIR imaging, indicating lesion or edema, was detected. No patient had cerebellar signs on clinical examination. The authors state, "Based on lack of detectable alterations in image analysis and clinical measures, we conclude that intraputaminal GDNF infused at putative therapeutic doses (30 micrograms/day) in excess of 1 year normally has no detectable effect on the human cerebellum." Transient striatal delivery of GDNF via encapsulated cells leads to sustained improvement in a bilateral model of Parkinson disease A Sajadi, JC Bensadoun, BL Schneider, C Lo Bianco, PA Aebischer Neurobiology of Disease 2006;22:119-129 Rats receiving GDNF from implanted cells maintain motor benefits after removal of the cells, according to this study. Rats bilaterally lesioned with 6-OHDA received bilateral implants of GDNF-secreting cells, or vehicle cells, within a porous polymer tube, one week after lesioning. The tube allows nutrients to flow in and GDNF to flow out, but prevents cell contacts with the host immune system. Time to complete a swimming protocol and a paw withdrawal protocol were compared between groups, and to non-lesioned, implanted rats. Results showed: --GDNF increased swimming and paw retraction velocity compared to vehicle in lesioned rats after 3 weeks of treatment. --Removal of transplanted GDNF-secreting capsules did not lead to worsening of movements for up to 6 weeks after removal. --GDNF treatment increased density of dopaminergic fibers in the denervated striatum, without increasing the number of nigral neurons, "strongly suggesting a regeneration process," according to the authors. "The sustained cellular and behavioral benefits after GDNF washout suggest the need for temporary delivery of the trophic factor," they state. "The inherent retrievability of encapsulated cells renders this technique attractive for clinical application." While pump-and-cannula delivery is also regulatable, current technology limits the volume of the striatum that can be treated. Therefore, they suggest, implanted cells may provide a better alternative for delivery of GDNF or other trophic factors. ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn