Preserving neuromuscular synapses in ALS by stimulating MuSK with a therapeutic agonist antibody

Cantor, Sarah; Zhang, Wei; Delestree, Nicolas; Remedio, Leonor; Mentis, George Z.; Burden, Steven J.

In amyotrophic lateral sclerosis (ALS) and animal models of ALS, including SOD1-G93A mice, disassembly of the neuromuscular synapse precedes motor neuron loss and is sufficient to cause a decline in motor function that culminates in lethal respiratory paralysis. We treated SOD1-G93A mice with an agonist antibody to MuSK, a receptor tyrosine kinase essential for maintaining neuromuscular synapses, to determine whether increasing muscle retrograde signaling would slow nerve terminal detachment from muscle. The agonist antibody, delivered after disease onset, slowed muscle denervation, promoting motor neuron survival, improving motor system output, and extending the lifespan of SOD1-G93A mice. These findings suggest a novel therapeutic strategy for ALS, using an antibody format with clinical precedence, which targets a pathway essential for maintaining attachment of nerve terminals to muscle.


  • thumnail for elife-34375-figures-v5.pdf elife-34375-figures-v5.pdf application/pdf 4.11 MB Download File

Also Published In

More About This Work

Academic Units
Pathology and Cell Biology
Published Here
August 11, 2018