Impaired prenatal motor axon development necessitates early therapeutic intervention in severe SMA
Lingling Kong, David Valdivia, Christian M. Simon, Cera W. Hassinan, Nicolas Delestrée, Daniel M. Ramos, Jae Hong Park, Celeste M. Pilato, Xixi Xu, Melissa Crowder, Chloe C. Grzyb, Zachary A. King, Marco Petrillo, Kathryn J. Swoboda, Crystal Davis, Cathleen Lutz, Alexander Stephan, Xin Zhao, Marla Weetall, Nikolai A. Naryshkin, Thomas O. Crawford, George Z. Mentis, Charlotte J. Sumner
Abstract
splice modifiers beginning immediately after birth in mice increased radial growth of the already myelinated axons, but in utero treatment was required to restore axonal growth and associated maturation, prevent subsequent neonatal axon degeneration, and enhance motor axon function. Together, these data reveal a cellular basis for the fulminant neonatal worsening of patients with infantile onset SMA and identify a temporal window for more effective treatment. These findings suggest that minimizing treatment delay is critical to achieve optimal therapeutic efficacy.