Session Information
Date: Thursday, June 23, 2016
Session Title: Parkinson's disease: Clinical trials, pharmacology and treatment
Session Time: 12:00pm-1:30pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: To describe the postmortem findings from two patients who underwent intraputaminal infusion of glial-derived neurotrophic factor (GDNF).
Background: GDNF has been shown to have neuroprotective and neuroregenerative effects in vitro, and antiParkinsonian effects in animal models. Intraputaminal infusion of GDNF in Phase I clinical trials showed mixed results. However, intraputaminal GDNF failed to reach its primary end point in a blinded, Phase II trial.
Methods: These patients were part of a ten patient cohort for an FDA-approved Phase I trial conducted in 2003. In this study, GDNF was continuously infused with dose-escalation through a unilateral intraputaminal catheter in patients with moderate to advanced idiopathic PD. The two patients described here completed one year of therapy before termination of the infusion.
Results: Here we report the pathological findings of two patients approximately one decade post intraputaminal GDNF infusion. Clinically, both patients had a significant improvement in motor scores by 6 months and 1 year of treatment, which was lost within 9 months of GDNF withdrawal. Unilateral administration of GDNF in the two patients did not demonstrate detectable long-term effects in terms of significant gliosis at the infusion site. There was no evidence of cerebellar lesions or Purkinje cell loss similar to what was seen in a preclinical primate toxicology study, which also supports the results of a prior MRI study of these patients. As expected, Lewy body pathology consistent with advanced PD was seen in both cases. One patient had a post-study course complicated by metastatic melanoma.
Conclusions: This is the first post-mortem study of GDNF intraputaminal infusion conducted at the University of Kentucky in 2003. Pathological and biochemical studies did not detect detrimental long-term effects from one year of intraputaminal GDNF infusion in the two patients studied.
To cite this abstract in AMA style:
T.R. Yamasaki, V.D. Smith, Y. Ai, D.M. Gash, P.T. Nelson, G.A. Gerhardt, J.T. Slevin. Pathological findings from two Parkinson’s disease patients after intraputaminal GDNF infusion [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/pathological-findings-from-two-parkinsons-disease-patients-after-intraputaminal-gdnf-infusion/. Accessed June 14, 2025.« Back to 2016 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/pathological-findings-from-two-parkinsons-disease-patients-after-intraputaminal-gdnf-infusion/