Background 

CDKL5 Deficiency Disorder (CDD) is a rare genetic condition that causes seizures and severe developmental challenges, often beginning in infancy. To understand the condition better, scientists use mouse models that have the same genetic change. While these CDD mice show some signs of the condition, they don’t always have spontaneous seizures, making it difficult for them to study. We wanted to test if these mice are more sensitive to seizures triggered by a loud sound that can trigger seizures similar to people with CDD. 

Research 

We studied mice with the CDD genetic change (both males and females) and compared them to normal mice. We exposed them to a loud noise on several occasions to see if it would trigger a seizure. We also implanted a small device in another group of CDD mice to monitor their brain activity and look for seizures happening on their own for over a week. 

We found that the CDD mice were extremely sensitive to loud sounds. The noise triggered severe seizures in most of the male CDD mice, and 80% of them developed seizures. The female CDD mice and the normal mice were mostly unaffected. When we monitored the CDD mice over time, we also discovered that a small number of them did have sudden, severe seizures on their own, without any trigger. 

Impact 

Our study shows for the first time that CDD mice are highly vulnerable to sound-triggered seizures. This can be harnessed to fast track the testing of treatments without having to wait to see if a small number of mice may develop seizures. This mouse model can now be used to test new treatments that could prevent these dangerous seizures and improve the lives of people impacted by these conditions.