Childhood dementias, a group of neurological disorders are characterised by neurocognitive decline, with physical and psychosocial impacts for individuals. With therapy available for <
5 % of childhood dementias, there is a high level of unmet need. Integration of biomarkers in clinical trials are important to characterize distinctive biological activities and interrogate targets for therapeutic development. This study reviewed four clinical trial registries to examine circulating biomarkers in childhood dementias. Findings from 262 studies were synthesized across 49/72 (68 %) childhood dementia disorders. Disease-related biomarkers were associated with 1) the primary pathophysiology 2) downstream pathogenic events 3) drug-related pharmacokinetics, safety and/or tolerability. The predominant biological measures were metabolites linked to the primary pathophysiological pathway (102 measures, 185 studies), while use of cytoskeletal proteins (3 measures, 15 studies), inflammatory mediators (19 measures, 24 studies), oxidative stress-related analytes (15 measures, 8 studies), neurotransmitters or related neuro-metabolites (3 measures, 5 studies) were limited. A range of potential biomarkers are used in clinical trials
however, their use is inconsistent and under utilised among conditions. Development of a panel of biomarkers has potential to interrogate and link shared biological pathways across the heterogeneity of childhood dementias to exert a significant impact for the development of disease-modifying therapies.