Researchers at the Francis Crick Institute in the United Kingdom have reported a novel approach to treat genetic epilepsy by replacing a missing enzyme in affected individuals. The work, published in Molecular Psychiatry, outlines a strategy focused on restoring the balance of neural enzymes to support healthier brain function.
Epilepsy in this context arises from a loss of function in the gene responsible for producing the CDKL5 enzyme, a complex protein that plays a key role in neuronal signaling. To explore whether boosting similar enzyme activity could improve outcomes for people with this condition, scientists conducted a series of experiments using laboratory mice. The aim was to determine if increasing the production of enzymes related to CDKL5 could mitigate seizures and enhance learning and social behaviors.
In the study, researchers used mice that did not produce the CDKL5 enzyme. These animals exhibited epilepsy-like seizure activity and showed difficulties in learning and social interaction, mirroring certain human symptoms. The team measured a biochemical process called phosphorylation, which involves attaching a phosphate group to other molecules and is essential for regulating protein activity. They focused on EB2, a molecule believed to reflect CDKL5-related activity in the brain. The findings showed that EB2 phosphorylation occurred even in mice lacking CDKL5, indicating that another enzyme could be compensating for the missing CDKL5 function.
Further investigation revealed that a CDKL5-like enzyme could target EB2 and is present in human neurons. Among the candidates, the enzyme CDKL2 emerged as a potential substitute that could influence EB2 activity in brain cells. This discovery suggests a plausible route for compensating CDKL5 deficiency by modulating CDKL2, which could form the basis of a future therapeutic approach for human epilepsy linked to CDKL5 loss.
Researchers are now focused on understanding how to safely stimulate brain cells to increase CDKL2 production without adverse effects. The overarching goal is to develop a treatment strategy that harnesses the brain’s own compensatory mechanisms to restore a healthier balance of neuronal signaling. While the work is in early stages, it opens the possibility of new interventions that could reduce seizure burden and improve cognitive and social outcomes for individuals affected by CDKL5-related epilepsy. Ongoing studies aim to translate these findings into safe, effective therapies that can be tested in clinical settings, offering hope for families and clinicians seeking better management options for this challenging condition.
These advances align with broader observations that link epilepsy with other neurodegenerative and developmental conditions, underscoring the need for a deeper understanding of how genetic factors shape brain excitability and resilience. The researchers emphasize that any potential therapy will require rigorous safety assessments and careful tuning to avoid unintended effects on neural networks. As the science progresses, collaborations across neuroscience, genetics, and clinical research will be essential to move promising lab findings toward real-world treatment options for patients in North America and beyond.