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Antibodies to GDNF Force Halt to All Clinical Trials (ANA 2004) E-MOVE reports from the 129th Annual Meeting of the American Neurological Association, held in Toronto October 2-6, 2004. SOURCE: E-Move Thursday, October 7, 2004 _ VOLUME 1 ISSUE 47 Multicenter, double-blind, randomized, placebo-controlled, parallel group trial of liatermin (rmetHuGDNF) administered by bilateral intraputaminal (IPu) infusion to subjects with idiopathic Parkinson’s disease AE Lang, S Gill, D Brooks, MA Brodsky, K Burchiel, RJ Coffey, A Dalvi, V Dhawan, WJ Elias, P Heywood, G Hotton, M Hutchinson, P Kelly, ER Laws, A Lozano, J Matcham, E Moro, J Nutt, NK Patel, R Penn, B Scott, M Stacy, AJ Stoessl, M Traub, D Turner, GF Wooten Platform presentation WIP 1 Results from the double-blind trial of intraputaminal GDNF indicate no clinical benefit from treatment. In addition, four patients developed anti-GDNF antibodies. In response, the manufacturer, Amgen, has withdrawn GDNF from all clinical trials. Thirty-four PD patients with disease duration averaging 9 years received placebo or GDNF by intraputaminal infusion via a catheter and implanted mini-pump. Promising results from a similar open-label trial were reported by E-MOVE and are archived at http://www.mdvu.org/emove/article.asp?ID=666 After 6 months, there was no difference between placebo and GDNF groups in either the primary endpoint (improvement from baseline in off-levodopa UPDRS motor score) or a variety of secondary endpoints, including total UPDRS score, walking tests, dyskinesia score, medication doses, quality of life measures, or off time. Fluorodopa uptake near the catheter tip was mildly but significantly improved in the GDNF-treated group. Adverse events were similar between the two groups, except for a slight increase in frequency of paresthesias, headache, and upper respiratory infection in GDNF-treated patients. In his platform presentation, Dr. Lang noted these results, which are at odds with the open-label trial results, emphasize the importance of blinded trials for surgical procedures, in which a strong and long-lasting placebo effect may occur. Given the benefit from GDNF seen in MPTP-treated primates, he also questioned the utility of that model for restorative therapies, versus its proven utility in testing symptomatic treatments. Four patients developed antibodies to GDNF during or after the double-blind phase of the trial, including one who developed them shortly after switching from placebo to open-label GDNF after the trial concluded. Three of these patients have GDNF- blocking antibodies, but the significance of this is unknown and the patients remain asymptomatic. In addition, two monkeys who have received unilateral intraputaminal GDNF have developed "unusual cerebellar cortical pathology," whose relationship to GDNF treatment is unknown. Amgen has withdrawn GDNF from all clinical trials due to safety concerns as a result of these developments. The trial was supported by Amgen and Medtronic SOURCE: E-Move Thursday, October 7, 2004 _ VOLUME 1 ISSUE 47 http://tinyurl.com/4xoq6 * * * ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn