Testing broad-spectrum and isoform-preferring HCN channel blockers for anticonvulsant properties in mice

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels have been implicated in the pathogenesis of epilepsy and consequently as targets for anticonvulsant drugs. Consistent with this, broad-spectrum block of HCN-mediated current (Ih) reduces seizure susceptibility in a variety of epilepsy models. However, HCN channel isoforms have distinct biophysical characteristics and anatomical expression suggesting that they may play different roles in setting neuronal excitability. Here we confirm that the broad-spectrum blocker ivabradine is effective at reducing seizure susceptibility in the s.c.PTZ seizure assay and extend this, showing efficacy of this drug in a thermogenic assay that models febrile seizures. Ivabradine is also effective at reducing thermogenic seizures in the Scn1a mouse model of Dravet syndrome in which febrile seizures are a feature. HCN isoform-preferring drugs were tested in the s.c.PTZ seizure assay. We confirm that the HCN4-preferring drug, EC18, is efficacious in reducing seizure susceptibility. Conversely, the HCN2/1-preferring drug, MEL55A, increased seizure susceptibility in the s.c.PTZ seizure assay. MEL57A, an HCN1-preferring drug, had no effect on seizure susceptibility. Mouse pharmacokinetic studies (for MEL55A and MEL57A) and screening against additional ion channels have not been thoroughly investigated on the HCN isoform-preferring compounds. Our results need to be considered in this light. Nevertheless, these data suggest that HCN isoform-selective block can have a differential impact on seizure susceptibility. This motivates the need to develop more HCN isoform-selective compounds to better explore this idea

Family Intervention for Empowerment Through Reading and Education, 2021-2022

The data were collected as part of the FIERCE project, investigating the effects of a reading programme on refugee children's educational trajectories. The data were collected from 322 Syrian refugee families living in Jordan (Amman and Al-Zaatari refugee camp) at three timepoints between February 2021 and May 2022. We collected a range of measurements on children's literacy, reading attitudes, socio-emotional learning, mental health and wellbeing; as well as the mothers' and fathers' reading attitudes, mental health and wellbeing, family dynamics and parenting (see the FIERCE data guide for detailed description). Additionally, we also collected data on children's and mothers' cognitive and emotional processing, mother-child interactions, and children's executive function.Community-led, shared book-reading interventions can improve early childhood development and reduce inequity. One such program, We Love Reading (WLR), was implemented in Jordan in response to the Syrian refugee crisis and involves mothers reading stories to children. This research project uses qualitative and quantitative methods to evaluate the potentially transformative nature of WLR among Syrian refugees in Jordan. Specifically, we interviewed stakeholders (Syrian refugee parents and 7-18 year old children) and conducted a randomised controlled trial with Syrian refugee mothers and their 4-8-year-old children. We use semi-structured interviews for the qualitative component. We use multiple methods in this wait-listed, randomized controlled trial - including survey measures, behavioural assessments, and participant observation - immediately before and immediately after the WLR intervention. The goal of this evaluation study is to understand how WLR may impact Syrian refugee children’s educational trajectories, literacy, and love of reading.</p