Gene therapy on mice SMA

On november 13, 2008 was published on the journal Human Molecular Genetics a new study by a swiss research group, led by Daniel Schümperli (Institute of Cell Biology at the University of Bern, Baltzerstrasse 4, CH-3012 Bern, Switzerland) entitled:

Rescue of a severe mouse model for Spinal Muscular Atrophy by U7 snRNA-mediated splicing modulation. 

Here the abstract:

In Spinal Muscular Atrophy (SMA), the leading genetic cause of early childhood death, the survival motor neuron 1 gene (SMN1) is deleted or inactivated. The nearly identical SMN2 gene has a silent mutation that impairs the utilisation of exon 7 and the production of functional protein. It has been hypothesised that therapies boosting SMN2 exon 7 inclusion might prevent or cure SMA. Exon 7 inclusion can be stimulated in cell culture by oligonucleotides or intracellularly expressed RNAs, but evidence for an in vivo improvement of SMA symptoms is lacking. Here we unambiguously confirm the above hypothesis by showing that a bifunctional U7 snRNA that stimulates exon 7 inclusion, when introduced by germ-line transgenesis, can efficiently complement the most severe mouse SMA model. These results are significant for the development of a somatic SMA therapy, but may also provide new means to study pathophysiological aspects of this devastating disease.

Here are some comments from the scientific world:

News published on Swissinfo.ch on november 14, 2008:

The cell biologist Daniel Schümperli and his team have found a way to correct the problem that leads to SMA through injections of genetically modified cells, able to synthesize the missing protein. The scientists have found significant improvements in function in mice suffering from the most severe form of the disease.
"This new study demonstrates for the first time that this approach leads to a significant reduction of symptoms of the disease", said Schümperli during the press conference today.

News published on the AFM website on november 17, 2008 (extract):

A group of swiss researchers led by professor Daniel Schümperli of University of Bern has managed, through a technique of gene surgery, to restore the production of SMN protein in the mouse model of spinal muscular atrophy, one of the most common childhood neuromuscular diseases. To achieve this, they used a U7 antisense RNA that can specifically recognize a portion of the gene (exon) avoiding the "elimination" in the mechanism of splicing. The symptoms of the disease have improved considerably in the treated mice, and in some cases, even disappeared. This work, partly funded by AFM thanks to donations of Telethon, was published on Human Molecular Genetics and is available on the website of the magazine.
Swiss researchers have noted an increase in the amount of SMN protein in the cells of these animals, related to an increase in their life expectancy and, in some of them, a normal muscle function with the possibility of reproduction for females.