Researchers at Cold Spring Harbor Laboratory (CSHL) and Isis Pharmaceuticals have devised a potential approach to treat the neuromuscular disease spinal muscular atrophy (SMA) caused by a deficiency in the survival of motor neuron protein (SMN) caused by a single gene mutation. SMA is a neurodegenerative disease of the motor neurons and results in progressive muscle weakness. It is also the leading hereditary cause of infant mortality. CSHL professor Dr. Adrian Krainer and his team have devised a method to stimulate cells to replenish the SMN protein by activating an existing, slightly modified copy of the mutant gene, survival of motor neuron 1, centromeric (SMN1). The researchers injected antisense oligonucleotides (ASO) into mice that had an added, human version of the SMN2 gene. As expected, the gene produced significantly more SMN RNA, including the section that is usually omitted, in tissues where the ASOs accumulate. These results highlight the therapeutic potential of some of these ASOs in the context of SMA. However, before this approach can be applied to human patients, several additional issues must be addressed-such as whether the ASOs really benefit growing animals with SMA and how and when they should be administered to affect the nervous system.


Références : Am J Hum Genet. 2008 Apr;82(4):834-48. Epub 2008 Mar 27.