2008 Barcelona - European Society of Human Genetics

Therapy for genetic disease
P10.26
Treatment of SMA fibroblasts and lymphoblasts with drugs that
increase smN expression reveals no responders and no additive
effects
E. Also-Rallo, L. Alias, L. Caselles, S. Bernal, R. Martínez, C. Soler-Botija, P.
Gallano, M. Baiget, E. F. Tizzano;
Hospital Sant Pau, Barcelona, Spain.
Spinal muscular atrophy (SMA) is a neuromuscular genetic disorder
caused by mutations in the SMN1 gene . The homologous copy
(SMN2) is always present in SMA patients . Exon 7 is spliced out of
most SMN2 transcripts (delta7) whereas SMN1 gene transcripts contain
mainly exon 7 (full-length) . Recent advances in SMA treatment
with pharmacologic agents have resulted in an increase in SMN mRNA
and protein levels in vitro . We performed a systematic analysis of SMN
expression in primary fibroblasts and lymphoblasts from 7 SMA patients
with varying clinical severity and different SMN1 genotypes to
determine expression differences in two accessible tissues (skin and
blood) . The basal expression of SMN mRNA full-length and delta7 in
fibroblasts and lymphoblasts at 24 and 48 hours was performed by
quantitative real time PCR. The ratio SMNFL/SMNΔ 7 was significantly
higher in control cells than in patients (p