Insulin-like growth factor-1 and neurotrophin-3 gene therapy prevents motor decline in an X-linked adrenoleukodystrophy mouse model  

Roberto Mastroeni (1), Jean-Charles Bensadoun (1), Delphine Charvin (1), Patrick Aebischer (1) *, Aurora Pujol (2, 3, 4), Cédric Raoul (1)

(1) Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
(2) Molecular Genetics, and Institute of Neuropathology, IDIBELL, 08907 Barcelona, Spain
(3) Center for Biomedical Research on Rare Diseases (CIBERER), Spain
(4) Catalan Institution of Research and Advanced Studies (ICREA) Barcelona, Spain
*Correspondence to Patrick Aebischer, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), SV BMI LEN, Station 15, CH-1015 Lausanne, Switzerland

Annals of Neurology 2009; vol. 66, pp. 117–122.

Abstract:  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.

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