Intraparenchymal spinal cord delivery of adeno-associated virus IGF-1 is protective in the SOD1G93A model of ALS.
The potent neuroprotective activities of neurotrophic factors, including insulin-like growth factor 1 (IGF-1), make them promising candidates for treatment of amyotrophic lateral sclerosis (ALS). In an effort to maximize rate of motor neuron transduction, achieve high levels of spinal IGF-1 and thus enhance therapeutic benefit, we injected an adeno-associated virus 2 (AAV2)-based vector encoding human IGF-1 (CERE-130) into lumbar spinal cord parenchyma of SOD1(G93A) mice. We observed robust and long-term intraspinal IGF-1 expression and partial rescue of lumbar spinal cord motor neurons, as well as sex-specific delayed disease onset, weight loss, decline in hindlimb grip strength and increased animal survival.
Lepore
Angelo C
AC
Department of Neurology, The Johns Hopkins University School of Medicine, 600 N. Wolfe St., Meyer 6-109, Baltimore, MD 21287, USA.
Haenggeli
Christine
C
Gasmi
Mehdi
M
Bishop
Kathie M
KM
Bartus
Raymond T
RT
Maragakis
Nicholas J
NJ
Rothstein
Jeffrey D
JD
D017668:Age of Onset; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D000229:Dependovirus / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007278:Injections, Spinal / Q000379:methods; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage* / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000378:metabolism; D011597:Psychomotor Performance / Q000502:physiology; D012737:Sex Factors; D013116:Spinal Cord / Q000502:physiology*; D013482:Superoxide Dismutase / Q000235:genetics; D013997:Time Factors; D014161:Transduction, Genetic
D018696:Neuroprotective Agents; D049452:Green Fluorescent Proteins; D007334:Insulin-Like Growth Factor I; C470429:SOD1 G37R protein, mouse; D013482:Superoxide Dismutase