This article provides further evidence of the promise of gene therapy to treat amyotrophic lateral sclerosis. In this work, Azzouz and colleagues utilized the ability of a lentivirus for remote delivery of a therapy to target the spinal cord, an area of the nervous system that has been difficult to target with standard drug therapies. This further supports the utility of retrograde viral gene delivery.

This work stems from a recent article showing that mice in which VEGF (vascular endothelial growth factor) levels were reduced by stress conditions developed ALS-like neuropathology. This suggested that VEGF might be a useful molecule to treat ALS, given evidence on VEGF’s ability to promote vascularization as well as neuroprotection.

Azzouz et al. used a lentivirus capable of retrograde transport that encoded the VEGF gene and they delivered this virus to different muscles of the SOD 1 mouse model of ALS. The results were quite dramatic: VEGF gene therapy slowed neurodegeneration of motor neurons and delayed the decline of motor function even when administered at the...  Read more

This article provides further evidence of the promise of gene therapy to treat amyotrophic lateral sclerosis. In this work, Azzouz and colleagues utilized the ability of a lentivirus for remote delivery of a therapy to target the spinal cord, an area of the nervous system that has been difficult to target with standard drug therapies. This further supports the utility of retrograde viral gene delivery.

This work stems from a recent article showing that mice in which VEGF (vascular endothelial growth factor) levels were reduced by stress conditions developed ALS-like neuropathology. This suggested that VEGF might be a useful molecule to treat ALS, given evidence on VEGF’s ability to promote vascularization as well as neuroprotection.

Azzouz et al. used a lentivirus capable of retrograde transport that encoded the VEGF gene and they delivered this virus to different muscles of the SOD 1 mouse model of ALS. The results were quite dramatic: VEGF gene therapy slowed neurodegeneration of motor neurons and delayed the decline of motor function even when administered at the time of overt disease symptoms. These results are quite similar to those obtained using a similar approach for retrograde gene delivery of insulin-like growth factor-1 (IGF-1) in the same ALS animal model (Kaspar et al., 2003), suggesting that delivery of trophic or neuroprotective factors is a viable approach for the treatment of ALS.

Indeed, these results are encouraging for clinical development. The EIAV vectors utilized for gene therapy have shown tremendous promise in preclinical studies. However, these particular vectors are in the earliest stages of development for the clinic. Clinical studies will require an assessment of safety in expanded animal studies and eventually patients. Nonetheless, this study provides additional evidence of the progress being made toward applying gene therapy research to the treatment of ALS and other neurodegenerative disorders.

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