Multiple Therapies May Be Needed to Treat ALS

Multiple therapies required? Treatment with an antibody targeting MuSK helped stabilize neuromuscular synapses in ALS model mice but motor neurons still degenerated. [Courtesy of James Sleigh, CC BY-NC 4.0].

Protecting nerve terminals may not be enough to treat ALS according to a new study. The report, led by Amy Easton at Genentech in San Francisco, California, found that treatment of ALS SOD1 G93A model mice with a muscle specific kinase (MuSK)-activating antibody preserved neuromuscular synapses – at least in the diaphragm. No improvement in respiratory function, however, could be detected. What’s more, the treatment did not promote the survival of motor neurons in the disease. The findings add to growing evidence that other treatment strategies may be needed to protect motor neurons against ALS (Gould et al., 2006; Frakes et al., 2017). The study appeared on December 4 in Neurobiology of Disease.


Sengupta-Ghosh A, Dominguez SL, Xie L, Barck KH, Jiang Z, Earr T, Imperio J, Phu L, Budayeva HG, Kirkpatrick DS, Cai H, Eastham-Anderson J, Ngu H, Foreman O, Hedehus M, Reichelt M, Hotzel I, Shang Y, Carano RAD, Ayalon G, Easton A. Muscle specific kinase (MuSK) activation preserves neuromuscular junctions in the diaphragm but is not sufficient to provide a functional benefit in the SOD1G93A mouse model of ALS. Neurobiol Dis. 2018 Dec 4. pii: S0969-9961(18)30397-8. [PubMed].

Cantor S, Zhang W, Delestrée N, Remédio L, Mentis GZ, Burden SJ. Preserving neuromuscular synapses in ALS by stimulating MuSK with a therapeutic agonist antibody. Elife. 2018 Feb 20;7. pii: e34375. [PubMed].

Pérez-García MJ, Burden SJ. Increasing MuSK activity delays denervation and improves motor function in ALS mice. Cell Rep. 2012 Sep 27;2(3):497-502. doi: 10.1016/j.celrep.2012.08.004. Epub 2012 Aug 30. [PubMed].

On the home page: nerve terminal. [Courtesy of Balice-Gordon, 1996, Current Biology.]


disease-als MuSK neuromuscular junction NMJ topic-preclinical
Share this: