[QUICK SUMMARY: Findings reported at the meeting of the Society for Neuroscience continue to support gene therapy with neural nutrients as a promising strategy in ALS.]
October 24, 2004
VEGF can be delivered into motor neurons by a viral vector injected into muscle, and can rescue the innervating nerve cells from ALS. Investigator Mimoun Azzouz PhD, director of neurobiology at Oxford BioMedica, detailed recently published findings showing a very significant increase in survival in SOD1 mice treated at disease onset with muscle injections of VEGF gene carried by a lentiviral vector. The treated mice survived on average for 146 days, compared to 127 days for controls. As measured by rotarod and footprint analysis, VEGF increased motor performance in these animals, Azzouz said in his talk at the Society for Neuroscience meeting. He added that his group has started meeting with experts in ALS to plan clinical testing.
Infusion of VEGF into the spaces of the brain can also rescue neurons and extends survival in mutant SOD rodents. Rats with the SOD1 mutation show a more rapid progress once the disease starts, compared to mice with the same gene change, said investigator Erik Storkebaum, Msc. Survival still increased despite the aggressive disease course in the rat model of ALS, said Storkebaum, of Flanders Interuniversity in Leuven, working with ALSA funded investigators including Dr. Wim Robberecht.
Storkebaum also showed results with mice that express abundant amounts of the receptor for VEGF after genetic engineering. When these mice are bred with SOD1 mutants, the result is better survival and motor performance. This suggests that VEGF may truly prove a boon for ALS. Whatever the mode of administration, it all gives a beneficial effect in ALS models, he said, adding that the group hopes the approach will work in ALS patients.
Nicholas Boulis of The Cleveland Clinic reported that IGF-1 delivery is another valid gene approach to ALS. Boulis, who is funded by ALSA, found that IGF-1 therapy induces neurons to extend fibers, and blocks the cascade inside the cell that causes motor neurons to die. IGF1 is capable of hitting the process of ALS at multiple levels, Boulis said.
Boulis said that IGF can extend survival out to 150 to 180 days, but only one percent of the therapeutic gene is reaching the spinal cord. Survival data have so far been variable across laboratories, he added. In ALS, retrograde transport may be malfunctioning, Boulis speculated. He said the investigators may still be below the dose range required for increased survival.
