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Persistent GDNF Expression 45 Months after Putaminal Infusion of AAV2-GDNF in a Patient with Parkinson's Disease.
Heiss, John D; Ray-Chaudhury, Abhik; Kleiner, David E; Ehrlich, Debra J; Scott, Gretchen; Edwards, Nancy A; Goldstein, David S; Hammoud, Dima A; Hadaczek, Piotr; Van Laar, Victor S; Graff, Shantelle A; Herscovitch, Peter; Lungu, Codrin; Hallett, Mark; Lonser, Russell R; Zaghloul, Kareem A; Bankiewicz, Krystof S.
Affiliation
  • Heiss JD; Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
  • Ray-Chaudhury A; Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
  • Kleiner DE; Laboratory of Pathology, National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland, USA.
  • Ehrlich DJ; Parkinson's Disease Clinic, Office of the Clinical Director, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
  • Scott G; Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
  • Edwards NA; Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
  • Goldstein DS; Autonomic Medicine Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
  • Hammoud DA; Center for Infectious Disease Imaging, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
  • Hadaczek P; Department of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
  • Van Laar VS; Department of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
  • Graff SA; Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
  • Herscovitch P; Positron Emission Tomography Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
  • Lungu C; Division of Clinical Research, and Office of the Clinical Director, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
  • Hallett M; Human Motor Control Section, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
  • Lonser RR; Department of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
  • Zaghloul KA; Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
  • Bankiewicz KS; Department of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
Mov Disord ; 2024 May 08.
Article in En | MEDLINE | ID: mdl-38718138
ABSTRACT

OBJECTIVE:

Gene therapy by convection-enhanced delivery of type 2 adeno-associated virus-glial cell derived neurotrophic factor (AAV2-GDNF) to the bilateral putamina seeks to increase GDNF gene expression and treat Parkinson's disease (PD).

METHODS:

A 63-year-old man with advanced PD received AAV2-GDNF in a clinical trial. He died from pneumonia after anterior cervical discectomy and fusion 45 months later. An autopsy included brain examination for GDNF transgene expression. Putaminal catecholamine concentrations were compared to in vivo 18F-Fluorodopa (18F-FDOPA) positron emission tomography (PET) scanning results before and 18 months after AAV2-GDNF infusion.

RESULTS:

Parkinsonian progression stabilized clinically. Postmortem neuropathology confirmed PD. Bilateral putaminal regions previously infused with AAV2-GDNF expressed the GDNF gene. Total putaminal dopamine was 1% of control, confirming the striatal dopaminergic deficiency suggested by baseline 18F-DOPA-PET scanning. Putaminal regions responded as expected to AAV2-GDNF.

CONCLUSION:

After AAV2-GDNF infusion, infused putaminal regions showed increased GDNF gene expression, tyrosine hydroxylase immunoreactive sprouting, catechol levels, and 18F-FDOPA-PET signal, suggesting the regenerative potential of AAV2-GDNF in PD. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Mov Disord Journal subject: NEUROLOGIA Year: 2024 Document type: Article Affiliation country: United States
Fulltext
Add to My VHL
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Mov Disord Journal subject: NEUROLOGIA Year: 2024 Document type: Article Affiliation country: United States