A premotor disease signature for Amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is the most frequent motoneuron disease with a devastating prognosis. A clinically established biomarker for an early or even premotor diagnosis of ALS is not available.

Due to the already advanced and rapidly developing disease stage at the time of diagnosis, an early and accurate diagnosis is mandatory for efficacious disease-modifying therapies. About 10% of all ALS patients have a genetic cause and can identify premotor gene mutation carriers (PGMC).

In this project, we will develop a clinico-molecular fingerprint of PGMC that will allow for a more timely diagnosis and shed light on its molecular pathogenesis.We will recruit subjects with mutations for ALS, but have not yet developed motor symptoms, symptomatic patients and control subjects.

All subjects will be asked to complete a detailed questionnaire and donate biological samples (blood, urine, tearfluid and CSF). Clinical data and indepth biofluid protoemics will be integrated to create a clinico-molecular fingerprint of PGMC.

Evaluations will be performed at an interval of one year to characterize the evolution of the fingerprint in ALS and control subjects.

Finally, the PGMC fingerprint will be tested in a validation cohort with pure motor symptoms, suspected of ALS, or one of its clinical mimics.We expect that the clinico-molecular fingerprint will improve diagnostic accuracy and also yield information about the pathophysiological causes driving ALS.