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--------- Forwarded message ---------- From: E-MOVE <[log in to unmask]> To: E-MOVE <[log in to unmask]> Date: Mon, 14 Oct 2002 20:11:14 GMT Subject: GDNF Restores Behavioral and Cell Function in PD Models Message-ID: <B0000017686@liquidus-www> 1. Chronic, controlled GDNF infusion promotes structural and functional recovery in advanced parkinsonian monkeys R Grondin, Z Zhang, A Yi, WA Cass, N Maswood, AH Andersen, DE Elsberry, MC Klein, GA Gerhardt, DM Gash Brain 2002;125:2191-2201 GDNF delivered via pump to the striatum or ventricles improves motor function and markers of dopaminergic cell function in monkeys, according to this study. Thirteen rhesus monkeys received unilateral MPTP injections, followed two months later by implantation of a minipump and catheter to deliver either vehicle (n=5) or glial cell line-derived neurotrophic factor to either the putamen (n=3) or the lateral ventricle adjacent to the striatum (n=5). The dose delivered was either 5 or 15 micrograms per day. Behavioral assessment via blinded videotape indicated a 30-60% improvement in parkinsonian disability versus baseline in treated, but not control, animals after 11 weeks, with no differences between the two sites of administration. Neurochemical assessment indicated a significant increase in dopamine and DOPAC, but not HVA, in the medial striatum on the lesioned side, but not in the intermediate or lateral portions further from the ventricle. On the unaffected side, significant increases were seen in HVA in all three portions. Compared to controls, treated animals had a five-fold increase in tyrosine hydroxylase-positive fibers in the periventricular region of the lesioned striatum, as well as increased perikaryal size of dopaminergic neurons. These effects were also seen on the unlesioned side. The authors argue that since at least two months elapsed between MPTP administration and GDNF delivery, their results are primarily attributable to the restorative, rather than neuroprotective, actions of GDNF. An editorial by Patrik Brundin accompanies the report. An E-MOVE meeting report on GDNF in PD patients is archived at http://www.wemove.org/emove/article.asp?ID=436 Here is the meeting report : Subject: Putaminal GDNF Administration, Retinal Epithelial Cells Improve PD Symptoms (AAN 2002) Date: 4/23/2002 E-MOVE reports from the 54th Annual Meeting of the American Academy of Neurology, April 13-20, in Denver Colorado. Poster numbers, session numbers, and pages are from Neurology 2002;58(supplement 7). 1. Intraparenchymal putaminal administration of glial-derived neurotrophic factor in the treatment of advanced Parkinson's disease SS Gil, NK Patel, K O'Sullivan, DJ Brooks, GR Hotton, C Svendsen, P Heywood S31.003, A241 Direct infusion of GDNF to the putamen improves symptoms of PD, according to this study. Five patients received GDNF to the putamen delivered via mini-pump and implanted cannula. At 12 months, off time was reduced, on time increased, and dyskinesias were improved. Total UPDRS off score declined from approximately 60 at baseline to approximately 35 at 12 months. The authors note their results are in contrast to a previous double-blind trial of intraventricular GDNF (http://www.wemove.org/emove/article.asp?ID=327). They suggest the difference may be due to the direct delivery to the putamen in this study. ------------------------------------------------------------------------- ------- 2. Neuroprotective and restorative effects of intrastriatal grafting of encapsulated GDNF-producing cells in a rat model of Parkinson's disease T Shingo, I Date, H Yoshida, T Ohmoto J Neurosci Research 2002;69:946-954 Implantation of encapsulated cells producing GDNF can mitigate the effects of 6-OHDA in a rat model of Parkinson's disease, according to this study. Rats received either control cells or GDNF-producing cells to the right striatum either 7 days before (Experiment 1) or 2-4 weeks after (Experiment 2) lesioning with 6-OHDA to induce unilateral parkinsonism. Compared to Exp 1 controls, apomorphine-induced rotation was reduced 92% in GDNF-treated animals. In Exp 2, rotation was reduced by approximately 30% in GDNF animals treated at 2 weeks post-lesion, but only 10% in those treated at 4 weeks. The number of tyrosine hydroxylase-positive fibers was significantly greater in GDNF-treated animals than in controls at all time points up to six months. Animals treated at 2 weeks post-lesion had more such fibers than those treated at 4 weeks. =======================================================================C opyright 2002 WE MOVE Editor: Richard Robinson ([log in to unmask]) This document may be freely redistributed by email only in its unedited form. We encourage you to share it with your colleagues. Visit http://www.wemove.org/emove for E-MOVE archives and information on subscribing to E-MOVE. To unsubscribe, visit http://www.wemove.org/emove/unsubscribe.asp. - WE MOVE 204 West 84th Street New York, NY 10024 TEL 800-437-MOV2 TEL 212-875-8312 FAX 212-875-8389 ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn