SMN2 and proximal spinal muscular atrophy: Upregulation of SMN protein levels improves motor function and life expectancy of SMA patients and animal models if achieved prior to onset of neuromuscular pathology and symptoms(13, 32, 86-88, 93), yet even high levels of SMN protein cannot correct neuromuscular junction defects once SMA has progressed to an advanced stage and loss of motor neurons upon cell death is irreversible.