John D Heiss1, Codrin Lungu2, Dima A Hammoud3, Peter Herscovitch4, Debra J Ehrlich5, Davis P Argersinger1, Sanhita Sinharay3, Gretchen Scott1, Tianxia Wu6, Howard J Federoff7, Kareem A Zaghloul1, Mark Hallett8, Russell R Lonser9, Krystof S Bankiewicz9,10. 1. Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. 2. Division of Clinical Research, and Office of the Clinical Director, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. 3. Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA. 4. Positron Emission Tomography Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA. 5. Parkinson's Disease Clinic, Office of the Clinical Director, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. 6. Clinical Trials Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. 7. Department of Neurology, University of California-Irvine, Irvine, California, USA. 8. Human Motor Control Section, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. 9. Department of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA. 10. Department of Neurological Surgery, University of California-San Francisco, San Francisco, California, USA.
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.
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 PDpatients. 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]FDOPAKis 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.
Authors: Hugo W A M de Jong; Floris H P van Velden; Reina W Kloet; Fred L Buijs; Ronald Boellaard; Adriaan A Lammertsma Journal: Phys Med Biol Date: 2007-02-14 Impact factor: 3.609
Authors: Krystof S Bankiewicz; Vivek Sudhakar; Lluis Samaranch; Waldy San Sebastian; John Bringas; John Forsayeth Journal: J Control Release Date: 2016-02-27 Impact factor: 9.776
Authors: Louisa C Johnston; Jamie Eberling; Philip Pivirotto; Piotr Hadaczek; Howard J Federoff; John Forsayeth; Krystof S Bankiewicz Journal: Hum Gene Ther Date: 2009-05 Impact factor: 5.695
Authors: J G Nutt; K J Burchiel; C L Comella; J Jankovic; A E Lang; E R Laws; A M Lozano; R D Penn; R K Simpson; M Stacy; G F Wooten Journal: Neurology Date: 2003-01-14 Impact factor: 9.910
Authors: Yohei Mineharu; Maria G Castro; Pedro R Lowenstein; Nobuyuki Sakai; Susumu Miyamoto Journal: Neurol Med Chir (Tokyo) Date: 2013-10-21 Impact factor: 1.742
Authors: Meihua Luo; Leo Kit Cheung Lee; Bo Peng; Chung Hang Jonathan Choi; Wing Yin Tong; Nicolas H Voelcker Journal: Adv Sci (Weinh) Date: 2022-07-18 Impact factor: 17.521
Authors: Pramod S Terse; Adrian P Kells; Patricia Noker; J Fraser Wright; Krystof S Bankiewicz Journal: Int J Toxicol Date: 2020-11-02 Impact factor: 2.032
Authors: Еlena V Mitroshina; Tatiana A Mishchenko; Olesya M Shirokova; Tatiana A Astrakhanova; Maria M Loginova; Ekaterina A Epifanova; Alexey A Babaev; Victor S Tarabykin; Maria V Vedunova Journal: Oxid Med Cell Longev Date: 2019-11-18 Impact factor: 6.543
Authors: Ana Fajardo-Serrano; Alberto J Rico; Elvira Roda; Adriana Honrubia; Sandra Arrieta; Goiaz Ariznabarreta; Julia Chocarro; Elena Lorenzo-Ramos; Alvaro Pejenaute; Alfonso Vázquez; José Luis Lanciego Journal: Int J Mol Sci Date: 2021-06-15 Impact factor: 5.923
Authors: Yaping Chu; Raymond T Bartus; Fredric P Manfredsson; C Warren Olanow; Jeffrey H Kordower Journal: Brain Date: 2020-03-01 Impact factor: 13.501
Authors: R Mark Richardson; Krystof S Bankiewicz; Chadwick W Christine; Amber D Van Laar; Robert E Gross; Russell Lonser; Stewart A Factor; Sandra K Kostyk; Adrian P Kells; Bernard Ravina; Paul S Larson Journal: J Neurol Neurosurg Psychiatry Date: 2020-07-30 Impact factor: 10.154