Negraes PD, Trujillo CA, Yu N-K, Wu W, Yao H, Liang N, Lautz JD, Kwok E, McClatchy D, Diedrich J, de Bartolome SM, Truong J, Szeto R, Tran T, Herai RH, Smith SEP, Haddad GG, Yates JR and Muotri AR.
Molecular Psychiatry, 2021
Summary:
Characterized by early-onset seizures, intellectual delay, and motor dysfunction, CDKL5 deficiency disorder is a neurodevelopmental condition whose precise targets remain unknown. Using patient-derived induced pluripotent stem cells, the authors generated neural cells. Several pathways, including cytoskeleton organization and glutamatergic synaptogenesis, were found to disrupted in patient-derived cells. CDKL5 deficiency disorder neurons demonstrated hyperexcitability on the MEA during development and increased synchrony. Using compounds selected from a drug screening platform, many parameters were able to be rescued. This approach may some day lead to new therapeutic opportunities for genetic epilepsy patients.
