New Gene Silencing Technique Promising in
Animal Studies Funded by The ALS Association
Roberta Friedman, Ph.D., ALSA Research Department Information Coordinator
March 13, 2005
A new approach that silences a specific gene linked to disease is giving hope for human treatment in preclinical testing for amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig’s disease). Two different research teams report encouraging results in a mouse model that mimics several aspects of the human disease.
“These studies are extremely exciting,” commented Lucie Bruijn, Ph.D., science director and vice president of The ALS Association (ALSA), “and provide a promising approach to treat familial forms of ALS linked to mutations in SOD1. As we learn more about the other genes involved in the disease a similar approach can be taken for those forms of ALS not linked to the SOD1 mutation.”
The mice express the mutant protein Cu/Zn Superoxide Dismutase (SOD1) responsible for some of the inherited forms of ALS.
The technique of RNA interference (ribonucleic acid interference or RNAi) interrupts the genetic instructions for making SOD1. Studies show a substantial increase in survival of these mouse models using RNAi together with a viral delivery system to target the cells involved in the disease.
ALSA-funded researchers from the Swiss Federal Institute of Technology and French collaborators reported March 13 in the advance online publication of Nature Medicine that ALS mice injected in the spinal cord with the RNAi therapeutic showed improved motor skills. The treated mice were better able to maintain swimming in a laboratory test, for about 20 days longer than untreated animals. At 120 days of age, mutant SOD1 mice take twice the time to swim to a platform as do normal mice. The treated mice had an improved swimming time of 50% as compared with the untreated group.
A British company, Oxford Biomedica Ltd. in Oxford, U.K., also published in the online advance for Nature Medicine using a similar viral delivery system. They demonstrated that muscle delivery of RNAi to silence the mutant SOD1 led to increased survival in the same mouse model system. Bruijn of ALSA noted that it is encouraging to see such rapid advancement of novel technologies such as RNAi by both the academic and biotech sector in therapeutic development for ALS.
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