Data in support of 2023 publication in eLife: An optogenetic cell therapy to restore control of target muscles in an aggressive mouse model of Amyotrophic Lateral Sclerosis

Breakdown of neuromuscular junctions (NMJs) is an early pathological hallmark of amyotrophic lateral sclerosis (ALS) that blocks neuromuscular transmission, leading to muscle weakness, paralysis and, ultimately, premature death. Currently, no therapies exist that can prevent progressive motor neuron degeneration, muscle denervation or paralysis in ALS. Here, we report important advances in the development of an optogenetic, neural replacement strategy that can effectively restore innervation of severely affected skeletal muscles in the aggressive SOD1G93A mouse model of ALS, thus providing an interface to selectively control the function of targeted muscles using optical stimulation. We also identify a specific approach to confer complete survival of allogeneic replacement motor neurons. Furthermore, we demonstrate that an optical stimulation training paradigm can prevent atrophy of reinnervated muscle fibers and results in a 10-fold increase in optically-evoked contractile force. Together, these advances pave the way for an assistive therapy that could benefit all ALS patients. 

The raw data and analysis files stored here were used to support the findings of this important study.