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Reprogramming epilepsy


Epilepsy is a heterogeneous condition that affects electrical activity in the brain and results in seizures. Whilst there are some treatments available for epilepsy, mesial temporal lobe epilepsy (MTLE) is treatment-refractory, leaving many people with unmanaged chronic seizures.

In a landmark new paper,  published in Cell Stem Cell, researchers have shown how reprogramming glia into interneurons can reduce chronic seizure activity. The study was led by Christophe Heinrich (Stem Cell and Brain Research Institute, INSERM), in collaboration with Benedikt Berninger and Nicolás Marichal from the Centre for Developmental Neurobiology, and others, to address a pressing question. 

Regenerative medicine is a rapidly growing field and reprogramming glial cells into clinically-relevant induced neurons is an emerging strategy for treating aberrant brain functioning. To be of therapeutic value, it is crucial that the induced neurons can promote functional recovery in the brain and restore balance in the networks. 

MTLE is associated with hippocampal seizures and degeneration of hipppocampal GABAergic interneurons. In their paper, Célia Lentini et al. use a mouse model of MTLE to express Ascl1 and Dlx2 in both reactive hippocampal glia in situ. This expression caused the glia to be successfully reprogrammed into induced neurons resembling interneurons.  Lentini et al. show how these interneurons functionally integrated into epileptic networks and were able to establish GABAergic synapses onto dentate granule cells. The authors also demonstrated how these mice had a significant reduction in both the number and duration of hippocampal seizures

Dr Christophe Heinrich, French National Institute of Health and Medical Research commented:

Our study uncovers glia-to-neuron reprogramming as a cell-based strategy to regenerate lost interneurons in epilepsy and to combat therapy-resistant seizures. We believe that glia-to-neuron reprogramming could serve as an innovative strategy also in the context of other devastating neurological disorders

This study, a milestone for regenerative medicine, demonstrates how glia-to-neuron reprogramming can be a potential therapeutic strategy that may help reduce seizures in treatment-resistant and treatment-refractory epilepsy.