Identification of a disease signature for premotor and early ALS.

Abstract-Text (inkl. Referenzen)

Introduction: Amyotrophic lateral sclerosis (ALS) is the most common motoneuron disease with a long diagnostic delay. Because of the rapid and fatal progression of ALS, early diagnosis is crucial to start therapy early and allow for inclusion in clinical trials. About 10% of ALS patients have a genetic cause. Genetic testing of their family members can identify subjects, who carry the mutation, but have not yet developed symptoms of the disease, so-called "pre-symptomatic gene mutation carriers" (PGMC). We aim to identify early ALS biomarkers already present in PGMC.

Method: For this study, 10 different countries join forces (Germany, France, Switzerland, Turkey, Slovakia, Israel, Sweden, Poland, Australia and USA). PGMC, control subjects and patients with suspicion for ALS (n=110 per group) will be recruited and longitudinally assessed over one year. Assessments include a medical history questionnaire, neurological examination, and the collection of biological samples (serum, plasma, urine, tear fluid, and CSF). Proteomic and metabolomic profiles will be analyzed by mass spectrometry and targeted immunoassays.

Results: The "premodiALS"-study secured funding within the JPND-call 2021 and received ethical approval. Recruitment will start in Q1/2023.

Discussion: A clinical and molecular ALS fingerprint would improve the timeliness and accuracy of diagnosis of ALS and ultimately lead to more effective treatment strategies.