Partially funded by FSMA, lead author Dr. F.D. Tiziano publishes a paper entitled, SMN transcript levels in leukocytes of SMA patients determined by absolute real-time PCR" in the European Journal of Human Genetics.

 The authors note that no reliable biomarkers are available to test the molecular efficacy of SMA treatments in clinical trials. At present, the only potential biomarker is the dosage of SMN products in peripheral blood, but the proof that SMN full-length (SMN-fl) transcript levels are reduced in leukocytes of patients compared with controls remains elusive (except for type I). In this study, the authors have developed a novel assay based on absolute real-time PCR, which allows the quantification of SMN1-fl/SMN2-fl transcripts. For the first time, they have shown that SMN-fl levels are reduced in leukocytes of type II–III patients compared with controls. We also found that transcript levels are related to clinical severity as in type III patients SMN2-fl levels are significantly higher compared with type II and directly correlated with functional ability in type II patients and with age of onset in type III patients. Moreover, in siblings having the same geneotype but with discordant phenotype, the less severely affected individuals showed significantly higher transcript levels.

From these data, the authors conclude that their study shows that SMN2-fl dosage in leukocytes can be considered a reliable biomarker and can provide the rationale for SMN dosage in clinical trials.

Please click here to read the paper abstract.