Assessment of nuclear gems quantity as a potential biomarker for evaluating the efficacy of drugs for spinal muscular atrophy.

Spinal muscular atrophy is a neuromuscular disorder caused by mutations in both copies of the survival motor neuron gene 1 (SMN1) which lead to reduction in the production of the SMN protein. Currently, there are several therapies that have been approved for SMA. Nonetheless, an urgent need to develop a new therapeutic approach is still of a high value as well as a powerful biomarker capable of assessing the effectiveness of SMA treatment, as a universally accepted one still has not been identified. This study aimed at investigating the quantity of gems in cell nuclei as a potential biomarker for SMA. Fibroblast cell cultures obtained from a patient with SMA type II and from a healthy individual were used to gain insight whether the number of gems in cell nuclei varies based on their SMN genotype and whether its increase is associated with therapeutic response. We discovered a remarkable difference in the number of gems in the nuclei of cells with different genotypes, specifically when counting gems per 100 nuclei. SMA fibroblasts were further treated with antisense oligonucleotides previously proved to have beneficial effects in correcting the abnormal splicing of SMN2 exon 7. We observed a significant increase in the number of gems in the treated cells compared to the intact SMA cells. The obtained results correlate significantly with the increase in full-length SMN transcripts level. Based on our findings, it is evident that the number of gems can be considered as a reliable biomarker for SMA drugs development.