Seizures-suppressant effect of encapsulated BDNF-producing cells in a rat model of temporal lobe epilepsy

One third of the epilepsies are refractory to medical treatment and, therefore, it is highly needed to find new therapies acting with mechanisms that are different from those of the drugs currently in use (Simonato et al., 2014). In this sense, neurotrophic factors like brain-derived neurotrophic factor (BDNF) may represent interesting candidates, because an extensive literature demonstrates their involvement in each of the cellular alterations associated with epileptogenesis: not only do their trophic effects suggest an involvement in cell death, neurogenesis and axonal sprouting, but they also exert effects at the synaptic level, with distinct modulatory actions at excitatory and inhibitory synapses (Simonato et al., 2006). However, BDNF has been reported to exert contrasting effects in epilepsy, depending on the period in the natural history of the disease and/or on specific alterations in some of its biological properties and/or on the delivery strategy. Thus, the therapeutic potential of BDNF for epilepsy is still controversial (Kuramoto et al., 2011; Simonato et al., 2006). Addressing the issue of BDNF therapeutic potential is further complicated by difficulties in its delivery. Here, we describe the effect on epileptic seizures of encapsulated cell biodelivery (ECB) devices filled with genetically modified human cells engineered to release BDNF into the host tissue. Encapsulated cells can survive long-term in the host tissue and ensure continued release of the therapeutic molecule (Emerich et al., 2014). Moreover, they hold the advantage of being a reversible treatment (Nikitidou et al., 2013).