ReCognitiON

Myotonic dystrophy type 1 (DM1), the most common adult form of muscular dystrophy, affects virtually all tissues; the noncurable condition carries significant morbidity and mortality impacting patient and family quality of life and socio-economic status. The OPTIMISTIC clinical trial has shown that Cognitive Behaviour Therapy (CBT), a patient-tailored intervention to increase activity and enable patients to deal with their disease, imparts significant beneficial impact on activity and participation. We now propose a multi-omic approach to identify the molecular signatures of the response to this clinical intervention, taking advantage of the thorough clinical characterization of the enrolled patients and the comprehensive set of serum samples at baseline and two follow-up time points. Our central hypothesis is that pathways associated with the positive response to CBT can be consolidated or reinforced by conventional drug therapies targeting the same pathways. A network-based bioinformatics approach shall be used to identify drug targets in the molecular signatures. We shall repurpose clinically approved drugs measuring impact on molecular profiles of patients cells and the behaviour of DM1 mouse models. Repurposed drugs with effects similar to CBT can be evaluated in isolation or combination with other treatments in future clinical trials for DM1 and other neurological conditions. The drug repurposing strategy based on the reverse engineering of a positive response to a behavioural intervention may set the scene for future drug development trajectories for rare diseases.