premodiALS
A premotor disease signature for ALS.

The premodiALS consortium is an initiative funded within the 2021 EU Joint Programme - Neurodegenerative Disease Research (JPND) call for proposals: "Linking pre-diagnosis disturbances of physiological systems to Neurodegenerative Diseases"
Amyotrophic lateral sclerosis (ALS) is the most frequent motoneuron disease with a devastating prognosis. Patients with ALS progressively lose their ability to voluntarily move their muscles. This includes muscles in the extremities, but also muscles responsible for respiration, swallowing and speech. Even today, it takes on average 12 months from the onset of motor symptoms to establish the diagnosis of ALS and approximately half of the patients are initially misdiagnosed. Although several molecules have been proposed as biomarker candidates, a clinically established signature for an early or even premotor diagnosis of ALS is not available. Due to the already advanced disease stage at the time of diagnosis as well as rapid disease progression, an early diagnosis is mandatory for efficacious disease-modifying therapies.
About 10% of all ALS patients have a genetic cause and genetic testing can identify premotor gene mutation carriers (PGMC) among family members of these familial ALS patients. PGMC are at risk to develop the disease due to the causative gene mutation, but have not yet developed motor symptoms.
In this project, we will develop a clinico-molecular fingerprint of PGMC that will shed light on the molecular pathogenesis of ALS and allow for a timelier diagnosis. We will recruit PGMC and control subjects through expert centers and their networks in Germany, France, Switzerland, Slovakia, Turkey, and Israel. Longitudinal data and CSF samples from gene carriers who have already developed motor symptoms of ALS will also be included.
All subjects will be asked to (1) complete a questionnaire about current and past clinical symptoms and environmental factors spanning the last 10 years of their life, to (2) donate biological samples (blood, urine, tear fluid, and CSF), and perform a smell test.
Tear fluid, blood plasma and CSF samples will be used to analyze the proteomic profile of the PGMC cohort using a combination of discovery mass spectrometry and targeted immunoassays. In addition, we will test for established biomarker candidates. Clinical data obtained in the questionnaire and molecular data will be integrated to create a clinico-molecular fingerprint of PGMC. Two evaluations will be performed at an interval of one year to characterize the evolution of the fingerprint in ALS and control subjects. Previously obtained data from multiple studies in ALS patients and control subjects will guide our analysis. Finally, the PGMC fingerprint will be subjected to biological validation on a cohort with pure motor symptoms, which comprises patients at very early stages of ALS, or one of its clinical mimics. This cohort will be collected in parallel at all clinical sites. We expect that the clinico-molecular fingerprint will not only improve diagnostic accuracy, but also yield information about molecular and pathophysiological causes driving ALS, ultimately empowering efficacious treatment strategies.

Interested in participation?
Download here our participant information for more information on how to contribute to premodiALS:
https://www.premodials.med.tum.de/sites/default/files/informationsflyer_premodials_27092022.pdf