RNA Silencing is able to Slow ALS Progress in Mice
October 24, 2004
ALSA funded investigators reported at the meeting of the Society for Neuroscience that silencing the readout of the mutant gene that causes inherited ALS can prolong the life of mice bearing the human mutation.
In a poster presentation, Cedric Raoul Ph.D., detailed the strategy for preventing the mutant gene from making protein in the ALS mouse. He and his colleagues devised a lentiviral vector to deliver the instructions to make a small molecule of RNA that would interrupt protein production of mutant SOD1. Injected into the spinal cord, the construct improved swimming ability of mutant mice, and also slowed onset of the signs of disease, as measured by muscle EMG signals. The mice were treated at 40 days of age, a time before their disease visibly affects their performance.
Raoul, who works at the Swiss Federal Institute of Technology with Patrick Aebischer, M.D., Ph.D., said that the RNA is able to stop known mutations to SOD1. He said the technology should enable treatment of other forms of ALS besides the inherited SOD1 version, once other responsible genes are found.
Aebischer said in a press conference at the meeting that the key is now to make RNA silencing a real therapy. The investigators are now trying to affect the whole spinal cord, he said, by packaging the silencing RNA into viruses to inject into muscle that will be carried back to the cord.
Commenting on the work at the press conference, Jeffrey Rothstein , M.D., Ph.D., of Johns Hopkins, said that silencing RNA is crucial to patients with familial ALS, as these patients progress so rapidly, dying on average in nine months following diagnosis.
ALSA Science Director Lucie Bruijn said that these very early results are exciting, but that the proof of principle needs to be expanded, by treating mice at the time of disease onset, to test efficacy at a time most relevant to human ALS.
