Restoring Bcl-x(L) levels benefits a mouse model of spinal muscular atrophy

Currently, no curative treatment is available for spinal muscular atrophy (SMA). Since the degeneration of spinal motor neurons in SMA is mediated by apoptosis, over-expression of an anti-apoptotic factor, Bcl-x(L), may benefit SMA. Here, we crossed a mouse model of SMA with Bcl-x(L) transgenic mice to create SMA/Bcl-x(L) mice. The Bcl-x(L) expression in the spinal neurons of SMA/Bcl-xL mice was nearly double that in SMA mice. SMA/Bcl-xL mice showed preserved motor function, normalized electrophysiological tests, diminished muscle atrophy, and less motor neuron degeneration. In addition, the life span of SMA/Bcl-x(L) mice was 1.5 times longer than that of SMA mice. Therefore, over-expression of Bcl-xL has a potential for amelioration of SMA, and Bcl-x(L), may be another attractive therapeutic target other than survival motor neuron (SMN) protein for use in future drug screening for SMA. (C) 2008 Elsevier Inc. All rights reserved.