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
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
Quintana-Sarti P, Higgins J, Reschke CR, …, Henshall DC
The Journal of Neuroscience, 46(11), e1081252025 · doi:10.1523/JNEUROSCI.1081-25.2025
Dr Mamad talks with FutureNeuro about researching CDKL5, a rare and severe genetic epilepsy, and what it means for families.
Media
"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 storyFunding
Dr Omar Mamad has received a new award with grant funding from FutureNeuro, the Research Ireland Centre for Translational Brain Science, to support the lab's work on CDKL5 Deficiency Disorder. The €128,800 award funds "The Broken GPS" — a project using single-place-cell recording to build the first cross-model atlas of how the brain's internal GPS breaks down across CDD, TLE, TBI, 22q11.2 deletion syndrome, and Dravet syndrome.
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.
