TY - JOUR
T1 - AAV2-mediated delivery of human neurturin to the rat nigrostriatal system
T2 - Long-term efficacy and tolerability of CERE-120 for Parkinson's disease
AU - Gasmi, Mehdi
AU - Brandon, Eugene P.
AU - Herzog, Christopher D.
AU - Wilson, Alistair
AU - Bishop, Kathie M.
AU - Hofer, Eva K.
AU - Cunningham, Justine J.
AU - Printz, Marie A.
AU - Kordower, Jeffrey H.
AU - Bartus, Raymond T.
PY - 2007/7
Y1 - 2007/7
N2 - Neurturin (NTN) is a neurotrophic factor with known potential to protect and restore the function of dopaminergic substantia nigra neurons whose degeneration has been most closely linked to the major motor deficits in Parkinson's disease (PD). CERE-120, an adeno-associated virus serotype 2 (AAV2)-based gene delivery vector encoding human NTN, is being developed as a potential therapeutic for PD. In a series of preclinical studies reported herein, CERE-120 delivery to the striatum produced a dose-related neuroprotection of nigrostriatal neurons in the rat 6-hydroxydopamine (6-OHDA) lesion model. Long-lasting efficacy of CERE-120 was evidenced by substantia nigra cell protection, preserved fiber innervation of the striatum, and behavioral recovery for at least 6 months. In addition, striatal infusion of CERE-120 was found to have a safety and tolerability profile devoid of side effects or toxicological responses, for at least 12 months post-treatment, even at dose multiples 125 times that of the lowest efficacious dose tested. These results support the ongoing CERE-120 clinical program in PD patients.
AB - Neurturin (NTN) is a neurotrophic factor with known potential to protect and restore the function of dopaminergic substantia nigra neurons whose degeneration has been most closely linked to the major motor deficits in Parkinson's disease (PD). CERE-120, an adeno-associated virus serotype 2 (AAV2)-based gene delivery vector encoding human NTN, is being developed as a potential therapeutic for PD. In a series of preclinical studies reported herein, CERE-120 delivery to the striatum produced a dose-related neuroprotection of nigrostriatal neurons in the rat 6-hydroxydopamine (6-OHDA) lesion model. Long-lasting efficacy of CERE-120 was evidenced by substantia nigra cell protection, preserved fiber innervation of the striatum, and behavioral recovery for at least 6 months. In addition, striatal infusion of CERE-120 was found to have a safety and tolerability profile devoid of side effects or toxicological responses, for at least 12 months post-treatment, even at dose multiples 125 times that of the lowest efficacious dose tested. These results support the ongoing CERE-120 clinical program in PD patients.
KW - 6-OHDA lesion
KW - Adeno-associated virus
KW - Gene delivery
KW - Glial cell line-derived neurotrophic factor
KW - Neurotrophic therapy safety
KW - Neurturin
KW - Parkinson's disease
KW - Toxicity
UR - http://www.scopus.com/inward/record.url?scp=34250336916&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34250336916&partnerID=8YFLogxK
U2 - 10.1016/j.nbd.2007.04.003
DO - 10.1016/j.nbd.2007.04.003
M3 - Article
C2 - 17532642
AN - SCOPUS:34250336916
SN - 0969-9961
VL - 27
SP - 67
EP - 76
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 1
ER -