BRIEF REPORT | doi:10.20944/preprints202309.1527.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: spinal muscular atrophy; SMN1 gene; SMN2 gene; nuclear gems; antisense oligonucleotides; splicing correction.
Online: 22 September 2023 (09:19:28 CEST)
Spinal muscular atrophy is a neuromuscular disorder caused by mutationsin 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, with much more undergoing active research. While various biomarkers have been proposed for assessing the effectiveness of SMA treatment, a universally accepted one still hasnot been identified. This study aimed to investigate whether the number of gems in cell nuclei could serve as a potential biomarker for SMA. To gain insight into whether the number of gems in cell nuclei varies based on their SMN genotype and whether the increase in gems number is associated with therapeutic response, we utilized fibroblast cell cultures obtained from a patient with SMA type II and from healthy individual. We have discovered a remarkable difference in the number of gems found in the nuclei of these cells, specifically when counting gems per 100 nuclei. Then the SMA fibroblasts were treated with antisense oligonucleotides the beneficial effects in correcting the abnormal splicing of SMN2 exon 7 have been demonstrated. It was observed that there was a significant increase in the number of gems in the treated cells compared to the intact SMA cells. The results obtained significantly correlate with an increase of full-length SMN transcripts share. Based on our findings, it is evident that the quantity of gems can be regarded as a reliable biomarker for SMA drugs development.
ARTICLE | doi:10.20944/preprints202302.0500.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: spinal muscular atrophy; newborn screening; SMN1; SMN2; real-time PCR; dried blood spots; SMA incidence; carrier frequency
Online: 28 February 2023 (03:45:16 CET)
Spinal muscular atrophy 5q (SMA) is the most common neuromuscular inherited disease in neonates which is associated with homozygous deletion of exon 7 in the SMN1 gene. Recently established drugs can improve the motor functions of SMA infants when treated in the pre-symptomatic stage. With aim of providing an early diagnosis, newborn screening (NBS) for SMA using real-time PCR assay with dried blood spots (DBS) was performed in Saint-Petersburg from January 2022 through November 2022. Here, 36,140 newborns were screened by GenomeX real-time PCR-based screening test, and three genotypes were determined. Homozygous deletion carriers (4 newborns), heterozygous carriers (772 newborns) and wild-type individuals (35,364 newborns) were identified. All four newborns screened positive for homozygous SMN1 deletion were confirmed by alternate methods. Two of the newborns had two copies of SMN2, and two of the newborns had three copies. We determined Saint-Petersburg spinal muscular atrophy incidence of 1 in 9,035 and SMA carrier frequency of 1 in 47. In conclusion, it can be summarized that providing both timely SMN1 information and confirmation along with SMN2 copy number as part of SMA newborn screening algorithm can significantly improve clinical follow-up, family members testing, and SMA patients' treatment.