A group of researchers may have found a potential target for the treatment of an inherited form of epilepsy. Researchers from the Francis Crick Institute, UCL, and MSD analysed mice devoid of the Cdk15 gene and employed phosphoproteomics to look for proteins that bind to the CDKL5 enzyme.
Rare forms of epilepsy that begin in early childhood are called developmental and epileptic encephalopathies. Seizures and delayed development are symptoms of CDKL5 deficiency disorder (CDD), one of the most prevalent forms of hereditary epilepsy. Since there are presently no treatments that target the condition, children with this disorder are treated with generic antiepileptic drugs.
The loss of function in CDD is related to a gene that produces the CDKL5 enzyme, which phosphorylates proteins--that is, it adds an extra phosphate molecule to the protein to change its activity. The exact mechanism by which genetic changes in CDKL5 lead to CDD remains unknown to researchers. They identified a calcium channel, Cav2.3, as a target. Cav2.3 allows calcium to enter nerve cells, exciting the cell and allowing it to pass on electrical signals. This is needed for the nervous system to function properly, but too much calcium coming into cells can result in overexcitability and seizures.