GSE52917

• This study demonstrated a surprisingly early occurrence of miRNA fingerprints associated with highly penetrant ALS mutations, even decades before the likely onset of disease. 
• Considering that earlier commencement of neuroprotective treatment is plausibly more effective and that, according to the results, molecular pathophysiology precedes the onset of disease for many years.
• The early, subclinical onset of molecular pathology provides also a possible explanation for the failure to substantially attenuate disease progression by disease-modifying treatment attempts in ALS to date.

• Another prominent finding of this study are the highly homogenous miRNA profiles in genetically-defined familial ALS patients and pre-manifest mutation carriers. 
• Moreover, 91.7% of the miRNAs downregulated in the mutation carriers overlapped with altered miRNAs in familial ALS.

• Riluzole (the only approved disease modifying ALS drug) is thought to delay degeneration of motor neurons primarily by a reduction of glutamate release and excitotoxicity but has only a modest effect on survival when treatment is started after onset of disease.

• To date, mutations in over 20 different genes have been implicated in ALS pathogenesis, with a hexanucleotide expansion in C9orf72 and mutations in the genes coding for SOD1, TARDBP and FUS being the most frequent.

• Although familial ALS comprises about 10–15% of all cases, the majority of ALS is considered sporadic without a known family history of ALS.

• In the ALS SOD1-G93A mouse model, for example, upregulation of muscle-specific miR-206 was evident in plasma even before the onset of symptoms (Toivonen et al., 2014), and miR-206 was shown to be involved in regeneration of neuromuscular synapses that slows down disease progression.
• Intraventricular delivery of an inhibitor of miR-155 (anti-miR-155), a miRNA that was upregulated in spinal cords of SOD1-G93A mice and patients with sporadic ALS, could significantly extend survival and disease duration of ALS model mice.

• Patients were considered sporadic cases based on a negative family history. 
• Additionally, the two most frequent known causes of familial ALS, namely mutations in the SOD1 gene and a hexanucleotide repeat expansion in C9orf72, were excluded by Sanger sequencing

• A classification model has been built using Trainset. The selected probes were:
  1. hsa-mir-1202_st
  2. hsa-mir-320a_st

• The model has been tested using Testset.