Prospective clinical trials to investigate clinical and molecular biomarkers

• Published in: Epilepsia (Copenhagen) Vol. 58; no. S3; pp. 20 - 26
• Main Authors: Auvin, Stéphane, Walker, Lauren, Gallentine, William, Jozwiak, Sergiusz, Tombini, Mario, Sills, Graeme J.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.07.2017
• Subjects: Animals; Antiepileptic agents; Biomarkers; Biomarkers - analysis; Clinical trials; Design; Disease Models, Animal; Epilepsy; Epilepsy - diagnosis; Epilepsy - physiopathology; HMGB1; HMGB1 protein; HMGB1 Protein - analysis; Humans; IL‐1β; Inflammation; Inflammation Mediators - analysis; Iron; Metabolism; Neurogenic Inflammation - diagnosis; Neurogenic Inflammation - physiopathology; Observational Studies as Topic; Prognosis; Prospective Studies; Prospective study; Randomized Controlled Trials as Topic; Seizures; Studies; Tuberous sclerosis; Biomarkers; Inflammation; HMGB1; IL-1β; Prospective study; Epilepsy
• ISSN: 0013-9580; 1528-1167
• DOI: 10.1111/epi.13782

Summary Among clinical studies, randomized studies as well as well‐designed observational studies are providing the highest quality data. In addition, these studies represent a good opportunity to examine biomarkers of ictogenesis and epileptogenesis. To date, no validated molecular or cellular biomarker exists for any aspect of epilepsy. We provide an overview of the inflammatory biomarkers under investigation in prospective clinical studies in epilepsy: proinflammatory cytokines in prolonged febrile seizure; High Mobility Group Box 1 (HMGB1) as a prognosis biomarker in epilepsy and the interaction between inflammation and metabolism, in particular, iron metabolism, in epilepsy. The designs of the European Union EPISTOP project following prospectively patients with tuberous sclerosis from birth to the start of the epilepsy and of the Standard and New Antiepileptic Drugs‐II study illustrate how such studies can be used to find new inflammatory biomarkers of ictogenesis and epileptogenesis. If we want to bridge the current gap between having numerous biomarker candidates from preclinical studies and their selective use in clinical practice, we need to explore multiple biologic systems, not just including inflammation. In addition, it is crucial that those involved in the design and support of relevant clinical studies recognize this gap and act accordingly, and in the interests of improving the diagnosis and prognosis for epilepsy.