25 November 2015 Today’s publication in Nature:
Yehezkel Sztainberg, Hong-mei Chen, John W. Swann, Shuang Hao, Bin Tang, Zhenyu Wu, Jianrong Tang, Ying-Wooi Wan, Zhandong Liu, Frank Rigo & Huda Y. Zoghbi (2015 November 25). Reversal of phenotypes in MECP2 duplication mice using genetic rescue or antisense oligonucleotides. Nature doi:10.1038/nature1615
Dr Zoghbi explains what they have accomplished in this video from the 401 project. Video created by Joseph Mendoza.
The article in Nature is what families have long been waiting and hoping for. It is extremely encouraging and suggests that the for some individuals that the symptoms of MECP2 Duplication Syndrome can be reversed, and for others the progress of the disorder can at least be arrested:
indicating that, at least in some cases, the neuroanatomy may remain sufficiently intact so that correction of the molecular dysfunction underlying these disorders can restore healthy physiology.
We find that antisense oligonucleotide treatment induces a broad phenotypic rescue in adult symptomatic transgenic MECP2
duplication mice (MECP2-TG) 19, 20, and corrected MECP2levels in lymphoblastoid cells from MECP2 duplication patients in a dose-dependent manner.
The finding that ASO treatment rescues the MECP2 duplication-like phenotypes to a similar extent as the genetic rescue provides a proof-of-concept about the value of this approach. To move this closer to translation, further studies will have to test different ASO dosages and establish the safety margin of MeCP2 levels, using a mouse model that exclusively expresses two human MECP2 alleles. Additionally, we will screen thousands of MECP2 ASOs for off-target effects.
While it is important to remember that reversing the syndrome does not mean that all the effects of the syndrome can be eliminated in every individual, this is incredibly positive news for everyone affected.
Thanks to the researchers and all those who have supported this research, and will help move this toward helping affected individuals.