Premium
Trial of magnetic resonance–guided putaminal gene therapy for advanced Parkinson's disease
Author(s) -
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.
Publication year - 2019
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.27724
Subject(s) - glial cell line derived neurotrophic factor , neurotrophic factors , tolerability , medicine , ciliary neurotrophic factor , magnetic resonance imaging , dopaminergic , adeno associated virus , parkinson's disease , nuclear medicine , vector (molecular biology) , chemistry , radiology , adverse effect , dopamine , disease , biochemistry , receptor , gene , recombinant dna
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 × 10 10 vg (n = 6); 3 × 10 11 vg (n = 6); and 9 × 10 11 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