Authors: Lauren Pulling
Researchers from the Karolinska Institutet (Stockholm, Sweden) and the University of Milan (Italy) have demonstrated that amyotrophic lateral sclerosis (ALS) neuronal degeneration may be reduced following treatment with IGF-2. Following observations that IGF-2 is present in degeneration-resistant oculomotor neurons, they successfully applied IGF-2 to non-resistant neurons in vitro and in vivo, indicating a potential new target for ALS treatment.
Previous research has shown that the progressive degeneration of motor neurons that characterizes ALS does not apply to oculomotor neurons, which appear to be relatively degeneration-resistant. In the search for genetic targets for new treatments, researchers have attempted to identify the genetic basis that underlies this resistance.
In this new study, published in Scientific Reports, the researchers focused on oculomotor neurons, finding that a growth factor is expressed in higher proportions in these neurons relative to those that degenerate. Lead researcher Eva Hedlund (Karolinska Institutet) explained: “We have now identified a factor, insulin-like growth factor 2, or IGF-2, within the resistant oculomotor neurons. We show that IGF-2 can rescue human motor neurons from degenerating.”
The team took skin cells from ALS patients and reprogramed them into stem cells, then cultivated them to differentiate into motor neurons. When treated with IGF-2, these neurons performed better than controls under stressful conditions.
Following this success in vitro, the researchers explored the effect of IGF-2 treatment in vivo. Mouse models of ALS were treated with IGF-2 via gene therapy: those treated with IGF-2 lived longer than controls. “We can see that motor neurons are preserved and that IGF-2 treatment causes the axons to regenerate and recreate vital connections with muscles that were previously lost,” added Hedlund.
The researchers hope that these observations could lead to new treatments to arrest the progress of ALS. While IGF-2 treatment has not been explored in the clinical setting, previous clinical studies in which IGF-1 was administered under the skin of ALS patients have produced contradictory results. However, these new findings indicate IGF-1 or IGF-2 treatment targeted directly at motor neurons via gene therapy could be successful.
Sources: Allodi I, Comley L, Nichterwitz S et al. Differential neuronal vulnerability identifies IGF-2 as a protective factor in ALS. Sci. Rep. doi:10.1038/srep25960 (2016) (Epub ahead of print); Karolinska Institutet press release