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Trial of magnetic resonance-guided putaminal gene therapy for advanced Parkinson's disease.
Heiss, John D; Lungu, Codrin; Hammoud, Dima A; Herscovitch, Peter; Ehrlich, Debra J; Argersinger, Davis P; Sinharay, Sanhita; Scott, Gretchen; Wu, Tianxia; Federoff, Howard J; Zaghloul, Kareem A; Hallett, Mark; Lonser, Russell R; Bankiewicz, Krystof S.
Afiliação
  • Heiss JD; Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, 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.
  • Hammoud DA; Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
  • Herscovitch P; Positron Emission Tomography Department, Clinical Center, 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.
  • Argersinger DP; Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
  • Sinharay S; Radiology and Imaging Sciences, Clinical Center, 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.
  • Wu T; Clinical Trials Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
  • Federoff HJ; Department of Neurology, University of California-Irvine, Irvine, California, USA.
  • Zaghloul KA; Surgical Neurology Branch, 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.
  • Bankiewicz KS; Department of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
Mov Disord ; 34(7): 1073-1078, 2019 07.
Article em En | MEDLINE | ID: mdl-31145831
ABSTRACT

OBJECTIVE:

To investigate the safety and tolerability of convection-enhanced delivery of an adeno-associated virus, serotype-2 vector carrying glial cell line-derived neurotrophic factor into the bilateral putamina of PD patients.

METHODS:

Thirteen adult patients with advanced PD underwent adeno-associated virus, serotype-2 vector carrying glial cell line-derived neurotrophic factor and gadoteridol (surrogate MRI tracer) coinfusion (450 µL/hemisphere) at escalating doses 9 × 1010 vg (n = 6); 3 × 1011 vg (n = 6); and 9 × 1011 vg (n = 1). Intraoperative MRI monitored infusion distribution. Patients underwent UPDRS assessment and [18 F]FDOPA-PET scanning preoperatively and 6 and 18 months postoperatively.

RESULTS:

Adeno-associated virus, serotype-2 vector carrying glial cell line-derived neurotrophic factor was tolerated without clinical or radiographic toxicity. Average putaminal coverage was 26%. UPDRS scores remained stable. Ten of thirteen and 12 of 13 patients had increased [18 F]FDOPA Kis at 6 and 18 months postinfusion (increase range 5-274% and 8-130%; median, 36% and 54%), respectively. Ki differences between baseline and 6- and 18-month follow-up were statistically significant (P < 0.0002).

CONCLUSION:

Adeno-associated virus, serotype-2 vector carrying glial cell line-derived neurotrophic factor infusion was safe and well tolerated. Increased [18 F]FDOPA uptake suggests a neurotrophic effect on dopaminergic neurons. © 2019 International Parkinson and Movement Disorder Society.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença de Parkinson / Terapia Genética / Dependovirus / Transtornos Parkinsonianos Limite: Adult / Female / Humans / Male Idioma: En Ano de publicação: 2019 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença de Parkinson / Terapia Genética / Dependovirus / Transtornos Parkinsonianos Limite: Adult / Female / Humans / Male Idioma: En Ano de publicação: 2019 Tipo de documento: Article