Professor Tom Gillingwater and Professor Simon Parson, at Edinburgh & Aberdeen Universities respectively, have found that the liver is a therapeutic target in SMA. The results of this investigation have been published in the Nature journal, Scientific Reports. This study was partly funded by The SMA Trust and SMA Europe, amongst others.
Decreased levels of SMN protein is associated with a range of problems around the body in people living with severe forms of SMA. Despite the presence of high levels of SMN protein in normal liver, there has not been any comprehensive study on the liver in SMA.
Gillingwater & Parson show that reduced SMN levels result in the failure of liver development, in a mouse model of severe SMA. The SMA liver is dark red, small and has the following characteristics: iron deposition; immature liver blood vessels, which are congested with blood; increased immature red blood cells; increased and persistent cells which release high levels of platelets, found as clot-like accumulations in the heart. The formation of blood cells in contrast, was unaffected. Further analysis revealed significant molecular changes in SMA liver, consistent with the morphological findings.
Treatment from birth with an antisense oligonucleotide (a molecule which allows the back-up gene, SMN2, to produce a greater amount of functional SMN protein), increased lifespan and ameliorated all morphological defects in the liver. Defects in the liver are evident at birth, prior to motor system pathology and impair essential liver function in SMA. The liver is a key recipient of SMA therapies and when antisense treatment is delivered throughout the body, this rescued the liver pathology. Liver therefore, represents an important therapeutic target in SMA.
E. Szunyogova, H. Zhou, G. K. Maxwell, R. A. Powis, F. Muntoni, T. H. Gillingwater & S. H. Parson. Survival Motor Neuron (SMN) protein is required for normal mouse liver development. Sci. Rep. 6, 34635; doi: 10.1038/srep34635 (2016).