CANDY

Comorbid Analysis of Neurodevelopmental Disorders and Epilepsy

Since mapping the entire human genome nearly 20 years ago, scientists have made tremendous progress in understanding the genetic basis of many human conditions, although there is never a one-to-one link between a single gene and a single condition. Several neurodevelopmental conditions often occur together or are associated with other somatic illnesses, this combination significantly affecting a person’s length and quality of life. To date, there are no effective treatments. The EU-funded CANDY project is following a trail of rare and common genetic variants that are shared in many neurodevelopmental conditions and the possibility that immune dysregulation and microbiome at some point play a role. Insight could point to personalised treatment and a drastic reduction in suffering for affected individuals. 

Neurodevelopmental disorders (NDDs) including autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and intellectual disability (ID) are clinically heterogeneous, often co-occur and affect ~15% of the EU population. Interestingly, NDDs are often associated with somatic illnesses (e.g. epilepsy, autoimmune and gastrointestinal disease) that lead to a significant increase in morbidity and mortality. For instance, the combination of ID and epilepsy in ASD is associated with a reduction in lifespan of ~20 years and an economic cost greater than cancer, stroke or dementia. Yet, the research on NDDs represents less than 1% of these other disorders leading to a lack of effective new treatments for NDDs and understanding of why they co-occur. Recent evidence showed that rare genetic variants increasing risk for NDDs are shared, converge on final common pathways (e.g. synaptic plasticity, glutamate and GABA neurotransmission and excitation/inhibition imbalance), and that a key role is likely played by immune dysregulation. CANDY’s innovation is to test, for the first time, if NDDs and their common mental and somatic multi-morbidity are caused by combination(s) of common and rare genetic variants and immune activation acting at different “sensitive periods”. Our multi-disciplinary team of world leading academics, patient organisations and SMEs will cost-effectively leverage existing EU-funded studies to 1) identify novel mechanisms underpinning NDDs and their multi-morbidity, 2) develop new strategies for prevention and treatment, 3) deliver novel biomarkers to guide early diagnosis, stratification and / or treatment monitoring and 4) provide open access databases, translational test batteries as well as tools and targets for valorisation. Together, CANDY will transform the landscape for people with NDDs and make possible personalised medicine approaches at different life stages.