Insulin-like growth factor-1 and neurotrophin-3 gene therapy prevents motor decline in an X-linked adrenoleukodystrophy mouse model.
X-linked adrenoleukodystrophy (X-ALD) is the most common inherited peroxisomal disorder characterized by a progressive demyelination of the central nervous system. The marked loss of myelin and oligodendrocytes observed in the disease prompted us to evaluate the therapeutic potential of insulin-like growth factor-1 and neurotrophin-3, two potent inducers of myelin formation and oligodendrocyte survival. Viral vectors engineered to produce insulin-like growth factor-1 or neurotrophin-3 were administrated into the cerebrospinal fluid of an X-linked adrenoleukodystrophy mouse model. We show that viral-based, long-lasting delivery of insulin-like growth factor-1 and neurotrophin-3 significantly halts the progression of the disease and leads to potent protective effect against the demyelination process. Ann Neurol 2009;66:117-122.
Mastroeni
Roberto
R
Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Bensadoun
Jean-Charles
JC
Charvin
Delphine
D
Aebischer
Patrick
P
Pujol
Aurora
A
Raoul
Cédric
C
D000074061:ATP Binding Cassette Transporter, Subfamily D; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000326:Adrenoleukodystrophy / Q000150:complications* / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D054422:Chemokine CCL22 / Q000172:deficiency; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000134:cerebrospinal fluid / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009069:Movement Disorders / Q000209:etiology* / Q000628:therapy*; D020933:Neurotrophin 3 / Q000134:cerebrospinal fluid / Q000235:genetics*
C508354:ABCD2 protein, mouse; D000074061:ATP Binding Cassette Transporter, Subfamily D; D018528:ATP-Binding Cassette Transporters; C515483:Ccl22 protein, mouse; D054422:Chemokine CCL22; D020933:Neurotrophin 3; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D007334:Insulin-Like Growth Factor I