Trancriptome biomarker discovery in ALS

Amyotrophic lateral sclerosis (ALS) is a devastating neuromuscular disorder leading to death within 2-5 years of disease onset. The most common genetic abnormality in ALS is a repeat expansion in the C9orf72 gene (c9ALS), which is found in familial ALS (fALS) and genetically unexplained ALS (sporadic ALS, sALS) cases. The development of therapies that effectively treat c9ALS or sALS is hindered by a lack of biomarkers to assess whether a drug is working. Similarly, diagnosis of sALS is only based on clinical presentation and confirmed as disease symptoms progress or after autopsy. We have performed experiments in blood to identify c9ALS- and sALS-specific defects in ribonucleic acids (RNA), biological molecules that determine what gene information is used to guide protein synthesis. We aim to extensively analyze this data to establish and validate a panel of disease-specific blood-based biomarkers that can be used to improve clinical diagnosis and accelerate development and testing of new therapies in clinical trials. The identification of biomarkers will allow characterization of ALS patients on the basis of their specific RNA profiles in order to facilitate screening for clinical trials, and potentially support earlier diagnosis. Furthermore, biomarkers linked to disease progression would allow more efficient assessment of drug efficacy in clinical trials than is possible with current clinical outcome measures. Therefore, our studies are of great importance to the field