We study how the loss of a single kinase reshapes the developing brain, and use that knowledge to find treatments for a rare, severe epilepsy.
CDKL5 Deficiency Disorder (CDD) affects roughly one in every 40,000 to 60,000 births. Children develop treatment-resistant seizures within months of birth, alongside profound developmental, motor, visual and sleep problems. Current care manages symptoms only. Our lab combines preclinical disease models with molecular profiling, chronic EEG and machine learning to map what goes wrong when CDKL5 is lost, and to test therapies that target the cause rather than the symptoms.
Dr Omar Mamad
Principal Investigator. Lecturer in Physiology and Medical Physics, RCSI. Funded Investigator, FutureNeuro.
What are the molecular, cellular, network, behavioural and systems-level impacts of CDD?
Can we develop non-invasive biomarkers to understand CDD and translate them to patients for improved diagnosis?
Can we develop disease-modifying treatments with fewer side effects that target multiple aspects of the disease?
Each project is led by a member of the team and tackles a different facet of CDKL5 Deficiency Disorder.
An open-source machine-learning and geometry pipeline that scores hind-limb clasping as reliably as trained humans, and picks up subtle movement differences in Cdkl5-deficient mice that standard scoring misses entirely.
VECTR-ClaspLed by Jordan Higgins
Uncovering altered mitochondrial function and metabolism in CDKL5 Deficiency Disorder.
Mitochondria-CDDLed by Erva Ghani
Turning a 150-year-old staining "artefact" into a label-free window on the neuronal nucleus, so nuclear shape and dendritic branching can be measured together in intact, unsectioned brain tissue.
Golgi-XRMLed by Jordan Higgins
Mapping how the loss of one kinase reshapes the coding and non-coding transcriptome of the brain.
RNA dysregulation-CDDLed by Samuel Egan
Testing whether dysregulated microRNAs are a therapeutic avenue to rescue deficits in behaviour, neuronal morphology and electrophysiology.
ASO-CDDLed by Jordan Higgins
Sleep disruption is one of the most burdensome features of CDD for families. Sleep-CDD asks why it happens and whether it can be treated.
Sleep-CDDLed by Eve Conheady
Examining the structure of neurons and the molecular mechanisms behind motor dysfunction.
Morphology-CDDLed by Joe Mernagh
CDKL5 is a kinase: it tags other proteins with a phosphate group. The animation follows those tags from the cilium and microtubules to the synapse, the ion channels and the nucleus, and shows what is lost when CDKL5 is missing.
How a microRNA is made, loaded into RISC and silences its target, and how an antimiR sequesters the microRNA so the protein is made again. This is the principle behind our ASO-CDD project.
During in vivo recordings a microcontroller sends the same pulse to the electrophysiology system and the cameras, so every spike and every video frame can be matched to the millisecond.
Villegas-Salmeron J, Egan S, Sanfeliu A, …, Mamad O
bioRxiv · doi:10.64898/2026.10.22.760890
Higgins J, Schneemann A, Cavanagh B, …, Mamad O
Brain Research Bulletin, 112142 · doi:10.1016/j.brainresbull.2026.112142
Di Sapia R, Bera A, Mamad O, …, Vezzani A
Epilepsia · doi:10.1002/epi.70453
Higgins J, Egan S, El‐Mansoury B, …, Mamad O
Epilepsia Open, 11(2), 670-678 · doi:10.1002/epi4.70240
Dr Mamad talks with FutureNeuro about researching CDKL5, a rare and severe genetic epilepsy, and what it means for families.
Lab news
We’re recruiting two Research Assistants to support our in vivo place-cell recordings in preclinical models of epilepsy, rare diseases and brain injury. Applications close on 15 October 2026.
Full storyMedia
"Research gives our CDKL5 community hope. We greatly value the dedication of Omar Mamad and his team in advancing our understanding of CDKL5. By bringing researchers, clinicians and families together, we can move closer to better treatments and a brighter future for those living with CDKL5." CDKl5 UK
Full storyPublication
Led by PhD student Jordan Higgins, the study describes a non-destructive workflow that reconstructs nuclear and dendritic architecture at the same time from intact brain tissue.
Full storyJoin a team at the frontier of genetic epilepsy research. Our lab combines expertise in non-coding RNA biology, in vivo electrophysiology and computational behaviour analysis to understand and ultimately treat genetic epilepsies, with a particular focus on CDKL5 deficiency disorder.
