However, although IGF-1 delivery to the spinal cord was massively improved by TTC domain, and it retained significant level of IGF-1 activity as measured by Akt phosphorylation, no positive effect could be demonstrated on the course of the disease in a mouse model of ALS either by intrathecal of intramuscular delivery [81]. Here, IGF1 is linked to amyotrophic lateral sclerosis.