The purpose of SMA Europe is to provide a framework to stimulate collaboration and accelerate translational research pathways in SMA and promote patient care.

  1. Characterization of post-transcriptional control mechanisms regulating SMN2 gene expression

    Principal investigator(s) :
    Dr. Margarida Gama Carvalho
    Institution :
    University of Lisbon, Portugal
    Grant :
    Grant Type:
    Operating Grant
    Call number :
    Start year :
    Duration :
    2 years
    Status :

    • Q. How is the expression of the SMN2 gene controlled?
    • A. It may be possible to develop drugs which act directly on SMN2 gene expression to increase the level of SMN protein.


    The “back-up” gene, SMN2, is able to produce SMN protein, but at insufficient levels to replace the loss of function of the SMN1 gene. Natural variations in the production of SMN protein form SMN2 are known to modulate disease severity, so understanding the mechanisms which regulate SMN2 gene expression should provide the basis for new therapies, with significant benefits for patients.


    Gene expression comprises several highly regulated steps, involving the production of a protein code (mRNA) for the DNA template, from which protein is made. Control at gene level can be considered the primary switch that turns the synthesis of a protein on or off. However,  previous work has shown that later evens, acting at the level of the protein code, can have a significant impact on the amount of protein produced from a given gene. Many of these control mechanisms have been shown to be amenable to efficient manipulation.Here, Dr, Carvalho looked at this further and developed highly specific molecules (morpholinos) that could be used to increase protein levels in patients. She confirmed the role of SMN2 mRNA regulation for protein levels and the potential of its manipulation for therapeutic developments; identified both regulators of the SMN2 mRNA and developed tool to identify expression of a particular gene and cell line models with great potential for drug screening. Dr. Carvalho also took the first steps towards in vivo manipulation of mRNA based on the results obtained in the study.