In two recently published papers, members of the Group NP&R showed that overexpression of Neuregulin 1, mediated by gene therapy, improved the evolution of the disease in the SOD1G93A mouse model of Amyotrophic Lateral Sclerosis (ALS). They suggest that this therapy could be considered in the future as a treatment for ALS.
In the first, an AAV vector was injected intravascularly to increase NRG1-type I in the mouse muscles. The results showed that SOD1G93A mice with higher levels of NRG1-I began to develop symptoms of the disease later, and had a slower disease progression than the controls. In addition, this therapy promoted an increase of the number of surviving motoneurons in the spinal cord compared to control mice, as well as improved preservation of their connections with skeletal muscles.
Mòdol-Caballero G, et al. Gene therapy for overexpressing Neuregulin 1 type I in skeletal muscles promotes functional improvement in the SOD1(G93A) ALS mice. Neurobiol Dis 2020; 137:104793. doi: 10.1016/j.nbd.2020.104793.
In the second paper, we used gene therapy based on intrathecal administration of AAV virus to overexpress NRG1-III in the spinal cord of SOD1G93A mice. Our results indicate that overexpression of NRG1-III preserved neuromuscular function of the hindlimbs, improved locomotor performance, increased the number of surviving MNs, and reduced glial reactivity in the treated female SOD1G93A mice. However, NRG1-III did not have a significant effect on male mice, indicating relevant sex differences.
Mòdol-Caballero G, et al. Therapeutic role of Neuregulin 1 Type III in SOD1-linked Amyotrophic Lateral Sclerosis. Neurotherapeutics 2020 in press. doi: 10.1007/s13311-019-00811-7.