Status epilepticus (SE) is a neurological emergency characterised by prolonged seizure activity or frequent seizures without recovery in between attacks. It is diagnosed clinically and requires prompt drug and supportive treatments to minimise risk of harm and death. Status epilepticus is estimated to account for 10% of epilepsy-related deaths [1], with one study showing a twelve-month mortality rate of 30% in adults [2].

Despite significant risk to personal health and broader societal and economic implications, the treatment of status epilepticus has remained relatively unchanged in the last two decades. Reasons for this are multiple, including costs associated with drug discovery and development.

Drug repurposing, the use of a licensed medication for a condition beyond the remit of its original application, would circumnavigate many of these challenges.

I hope to explore drug repurposing in the setting of status epilepticus using a genomics-based approach. This centres on the premise that alterations in gene expression (so called “genetic signatures”) are seen in SE [3], and that if reversed by select treatments, seizure cessation would occur [4,5].

Using common genetic changes (“signatures”) that have been found to occur in early SE, I aim to use publicly-available molecular databases to identify currently used drugs that would hypothetically restore these genetic changes to their norm (in-silico). I would then look to determine if these findings can be replicated in cultured neuronal cells in which SE has been induced (in-vitro).

I hope to build on current knowledge of drug-repurposing in epilepsy, with particular attention paid to recognising currently-used medications that demonstrate in-vitro efficacy in SE. Success would pave the way for in-vivo study and ultimately clinical trial in patients with epilepsy.

References

1. Trinka E, Rainer LJ, Granbichler CA, Zimmermann G, Leitinger M. Mortality, and life expectancy in Epilepsy and Status epilepticus—current trends and future aspects. Frontiers in Epidemiology. 2023 Feb 23;3.
2. Choi SA, Lee H, Kim K, Park SM, Moon HJ, Koo YS, et al. Mortality, Disability, and Prognostic Factors of Status Epilepticus: A Nationwide Population-Based Retrospective Cohort Study. Neurology. 2022 Sep 27;99(13):e1393–401.
3. Henshall DC. Epigenetic changes in status epilepticus. Epilepsia. 2018 Aug 29;59(S2):82–6.
4. Walker MC. Drug repurposement in Status Epilepticus. 2024.
5. Mirza N, Sills GJ, Pirmohamed M, Marson AG. Identifying new antiepileptic drugs through genomics-based drug repurposing. Hum Mol Genet. 2017 Feb 1;26(3):527-537.