Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease and the most common inherited cause of infant mortality. SMA, with a carrier frequency of ∼1:40, affects ∼ 1:8,000 births. In severe cases, death usually ensues within the first two years of life. There are currently no therapeutic treatments for SMA other than supportive care. At a molecular level, SMA is caused by insufficient levels of the survival motor neuron (SMN) protein. Our group recently reported on the discovery and optimization of a new series of small molecules, represented by ML372, with good potency, pharmacokinetics, tolerance, and CNS penetration that are able to increase levels of SMN protein in several model cell lines (Xiao, J. et al., J. Med. Chem., 2011, 54, 6215-6233.). Herein, we characterize the ability of ML372 to increase SMN protein levels in vivo, restore motor function, and prolong survival of SMNΔ7 SMA Mice.