Encapsulated cell therapy for epilepsy: long-term, stable and efficacious targeting of the hippocampus with GDNF

Contemporary antiepileptic drugs are ineffective in approximately 30% of the patients. These patients continue to experience seizures and, in many cases, seizures increase in frequency and are associated with significant cognitive decline and psychiatric disorders (Lin et al., 2012). The local delivery to the CNS of trophic factors like glial cell line-derived neurotrophic factor (GDNF) has tremendous potential for treating a range of diseases, including epilepsy. However, systemic administration of GDNF cannot allow targeted and site-specific delivery. We have developed a delivery system that ensures high levels of GDNF to the epileptogenic area in a selective, long-term and stable manner. This system is based on implanting trophic factor-secreting cells encapsulated (EC) in a biocompatible matrix and separated from the host brain tissue by a polymer membrane. Therefore, this technology platform combines the potency of de novo, in situ synthesis of cell-derived GDNF with the safety of an implantable, biocompatible, and retrievable medical device (Emerich et al., 2014; Karami et al., 2015; Walhberg et al., 2012).