Contemplating stem cell therapy for epilepsy-induced neuropsychiatric symptoms

Abstract

Epilepsy is a debilitating disease that impacts millions of people worldwide. While unprovoked seizures characterize its cardinal symptom, an important aspect of epilepsy that remains to be addressed is the neuropsychiatric component. It has been documented for millennia in paintings and literature that those with epilepsy can suffer from bouts of aggression, depression, and other psychiatric ailments. Current treatments for epilepsy include the use of antiepileptic drugs and surgical resection. Antiepileptic drugs reduce the overall firing of the brain to mitigate the rate of seizure occurrence. Surgery aims to remove a portion of the brain that is suspected to be the source of aberrant firing that leads to seizures. Both options treat the seizure-generating neurological aspect of epilepsy, but fail to directly address the neuropsychiatric components. A promising new treatment for epilepsy is the use of stem cells to treat both the biological and psychiatric components. Stem cell therapy has been shown efficacious in treating experimental models of neurological disorders, including Parkinson’s disease, and neuropsychiatric diseases, such as depression. Additional research is necessary to see if stem cells can treat both neurological and neuropsychiatric aspects of epilepsy. Currently, there is no animal model that recapitulates all the clinical hallmarks of epilepsy. This could be due to difficulty in characterizing the neuropsychiatric component of the disease. In advancing stem cell therapy for treating epilepsy, experimental testing of the safety and efficacy of allogeneic and autologous transplantation will require the optimization of cell dosage, delivery, and timing of transplantation in a clinically relevant model of epilepsy with both neurological and neuropsychiatric symptoms of the disease as the primary outcome measures.

Adenosine Kinase, a Common Pathologic Biomarker for Human Pharmacoresistant Epilepsy

“…Currently, more and more experimental and clinical research demonstrated the bidirectional relation between epilepsy and associated comorbidities [61][62][63]. Patients with epilepsy, especially with disabling epilepsy, clinically demonstrate not only recurrent seizures, cognition deficits and psychiatric symptoms such as depression and psychosis.…”

Partial depletion of septohippocampal cholinergic cells reduces seizure susceptibility, but does not mitigate hippocampal neurodegeneration in the kainate model of epilepsy

“…Firstly, it is likely that this process can be initiated due to the loss of either hippocampal GABAergic interneurons (Sloviter, 1987), which would prompt axon outgrowth aimed to establish connections with new target cells, or septal parvalbumin-containing cells (also GABAergic) (Sanabria et al, 2006), which would disinhibit local circuits within the MS/DB. Should this be the case, implementation of recently developed novel treatment strategies based on stem cell therapy, in particular transplantation of GABAergic precursor cells (Lippert et al, 2018;Rao et al, 2017;Yasuhara et al, 2013), may lead to restoration of the septohippocampal projection system, thereby removing excessive cholinergic drive upon dentate molecular layer. Another possibility is that fiber sprouting can be triggered by neuroinflammatory signalling.…”

Models for discovery of targeted therapy in genetic epileptic encephalopathies

“…Stem cell-based therapeutic approaches have been reported in different neurological diseases including stroke, multiple sclerosis, and Parkinson's disease, but have also been explored as a potential treatment for epilepsy (Rao et al 2017). Many studies focused on repairing and enhancing the GABAergic system by transplantation of GABAergic progenitor cells into epileptic brain regions .…”