Muscular MiRNA in SMA: use as biomarkers and therapeutics
Spinal muscular atrophy(SMA) is a relatively rare genetic disease characterized by progressive muscular atrophy, flaccid paralysis, normal intellectual development. Prognostic biomarkers are important to evaluate and hopefully predict the response to the treatment dedicated to patients. This Patent concerns the analysis and the development of an ad hoc method for the determination of 3 microRNA levels in serum samples from patients and controls. Serum levels of these miRNAs are related to the severity of the patient’s condition. This makes them promising biomarkers for SMA.
The three miRNAs were significantly over-expressed in SMA patients, and showed a correlation with the severity of the condition. In addition, the sum of the three miRNA levels allows us to distinguish patients and controls with high sensitivity and specificity. Finally, the potential therapeutic role of modulation of these in SMA mouse models was evaluated. Inhibition of miR181a-5p has determinated an increase in the survival of treated animals compared to controls.
The availability of effective treatments has made it increasingly urgent to identify reliable prognostic biomarkers, biomarkers that allow to establish the clinical severity of patients and to monitor the effects of treatment and identify the subjects with greater probability of response.
- The identification of these 3 miRNAs as sensitive and specific prognostic biomarkers for SMA provides a reliable, reproducible and easy-to-use in vitro method for evaluating the prognosis of SMA, monitoring its development and the efficacy of a treatment;
- The use of anti-miR-181a-5p can be thought as a combinatorial treatment, in association with compounds modulating SMN levels in patients.
- The use of absolute qRT-PCR for the quantification of serum miRs levels has reduced experimental variability compared to commercially available relative assays;
- Our data have been obtained from human samples, differently from those published, from cell cultures or pre-clinical models;
- We provide evidence of the role of skeletal muscle in the pathophysiology of SMA.