Mitochondrial function and metabolic dysfunction in CDD
Uncovering altered mitochondrial function and metabolism in CDKL5 Deficiency Disorder.
Mitochondria-CDDLed by Erva Ghani
Understanding CDKL5 Deficiency Disorder, from molecule to seizure.
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.
Why we do this
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.
- 25
- Publications
- 5
- Active projects
- 7
- Team members
Dr Omar Mamad
Principal Investigator. Lecturer in Physiology and Medical Physics, RCSI. Funded Investigator, FutureNeuro.
Three questions drive the lab
- 01
Understanding the disease
What are the molecular, cellular, network, behavioural and systems-level impacts of CDD?
- 02
Biomarkers
Can we develop non-invasive biomarkers to understand CDD and translate them to patients for improved diagnosis?
- 03
Therapeutics
Can we develop disease-modifying treatments with fewer side effects that target multiple aspects of the disease?
Current projects
Each project is led by a member of the team and tackles a different facet of CDKL5 Deficiency Disorder.
Modelling RNA dysregulation for therapeutic and biomarker discovery
Mapping how the loss of one kinase reshapes the coding and non-coding transcriptome of the brain.
RNA dysregulation-CDDLed by Samuel Egan
Sleep disturbances in the pathophysiology of CDD
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
Neuron morphology and its molecular basis in CDD
Examining the structure of striatal neurons and the molecular mechanisms behind motor dysfunction.
Morphology-CDDLed by Joe Mernagh
Selected publications
Aug 2026Journal article
Temperature homeostasis disruption and hypothalamic alterations in experimental drug‐resistant epilepsy
Di Sapia R, Bera A, Mamad O, …, Vezzani A
Epilepsia · doi:10.1002/epi.70453
Apr 2026Journal article
Loss of cyclin‐dependent kinase‐like 5 results in susceptibility to audiogenic seizures in mice
Higgins J, Egan S, El‐Mansoury B, …, Mamad O
Epilepsia Open, 11(2), 670-678 · doi:10.1002/epi4.70240
Mar 2026Journal article
Attenuated Single Neuron and Network Hyperexcitability Following MicroRNA-134 Inhibition in Mice with Drug-Resistant Temporal Lobe Epilepsy
Quintana-Sarti P, Higgins J, Reschke CR, …, Henshall DC
The Journal of Neuroscience, 46(11), e1081252025 · doi:10.1523/JNEUROSCI.1081-25.2025
Feb 2026Preprint
VECTR-Clasp: An open machine-learning and vector-based framework for objective quantification of motor dysfunction during hind-limb clasping in Cdkl5-deficient mice
Higgins J, Egan S, Harrison K, …, Mamad O
bioRxiv, 2026.02.25.707643 · doi:10.64898/2026.02.25.707643
In conversation
Dr Mamad talks with FutureNeuro about researching CDKL5, a rare and severe genetic epilepsy, and what it means for families.
Latest from the lab
Funding
New Research Ireland award to study sleep disturbances in CDKL5 Deficiency Disorder
Sleep-CDD, a four-year programme running to 2030, will investigate why sleep is disrupted in CDD and whether restoring it can improve seizures and development.
Full storyPublication
Epilepsy disrupts the brain's temperature control, new study in Epilepsia shows
Work with collaborators reveals hypothalamic neuronal loss, inflammation and thyroid axis changes in experimental temporal lobe epilepsy.
Full storyPublication
First report of sound-triggered seizures in a CDKL5 mouse model
Published in Epilepsia Open, the study establishes audiogenic seizure susceptibility as a highly penetrant phenotype in Cdkl5 knockout mice.
Full storySupported by
- Research Ireland
- SFI-IRC Pathway Programme
- FutureNeuro
- RCSI
- CDKL5 Ireland
- CDKL5 UK
- Loulou Foundation / Orphan Disease Center, University of Pennsylvania
- CDKL5 Alliance
Work with us
Join 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.
