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Advanced Neurology mTOR inhibition in epilepsy

compared to none in the placebo group. 106 Metformin 2. Corrales-Hernández MG, Villarroel-Hagemann SK,
was well-tolerated, with no cases of hypoglycemia, lactic Mendoza-Rodelo IE, et al. Development of antiepileptic
acidosis, or treatment-related serious adverse events. drugs throughout history: From serendipity to artificial
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The authors concluded that although metformin may be intelligence. Biomedicines. 2023;11(6):1632.
less potent than rapamycin or everolimus, it offers several doi: 10.3390/biomedicines11061632
advantages, such as a more favorable safety profile and 3. Van Hugte EJH, Schubert D, Nadif Kasri N. Excitatory/
fewer drug-drug interactions, without interfering with inhibitory balance in epilepsies and neurodevelopmental
the metabolism of other mTOR inhibitors or antiseizure disorders: Depolarizing γ-aminobutyric acid as a common
medications. The authors also raised the possibility of mechanism. Epilepsia. 2023;64(8):1975-1990.
106
combined therapy using metformin and a more potent doi: 10.1111/epi.17651
mTOR inhibitor, which could allow for lower doses of the
mTOR inhibitor, thereby minimizing side effects. 106 4. D’Antuono M, Köhling R, Ricalzone S, Gotman J, Biagini G,
Avoli M. Antiepileptic drugs abolish ictal but not interictal
8. Conclusion epileptiform discharges in vitro. Epilepsia. 2010;51(3):423-431.

In this review, we provide a comprehensive overview doi: 10.1111/j.1528-1167.2009.02273.x
of the mTOR signaling pathway, outline the spectrum 5. Sun L, Zheng X, Liu C, Shi M, Lv Y. The detection of the
of mTORopathies and GATORopathies, and highlight negative effects of interictal epileptiform discharges on
the clinical use of mTOR inhibitors and other potential cognition: An event-related potential study. J Nerv Ment Dis.
mTOR-modulating agents. Modulation of the mTOR 2019;207(3):209-216.
pathway holds promise for providing anti-epileptogenic doi: 10.1097/NMD.0000000000000945
and disease-modifying effects in mTORopathies, with the
potential to reverse underlying neuropathology. 6. Myers CT, Mefford HC. Advancing epilepsy genetics in the
genomic era. Genome Med. 2015;7(1):91.
Acknowledgments doi: 10.1186/s13073-015-0214-7
None. 7. Sadowski K, Kotulska-Jóźwiak K, Jóźwiak S. Role of
mTOR inhibitors in epilepsy treatment. Pharmacol
Funding Rep. 2015;67(3):636-646.
None. doi: 10.1016/j.pharep.2014.12.017

Conflict of interest 8. Hodges SL, Lugo JN. Therapeutic role of targeting mTOR
signaling and neuroinflammation in epilepsy. Epilepsy Res.
The authors declare that they have no competing interests. 2020;161:106282. doi:10.1016/j.eplepsyres.2020.106282
Author contributions 9. National Center for Biotechnology Information
(NCBI). Available from: https://pubmed.ncbi.nlm.nih.
Conceptualization: All authors gov/?term=mtor&sort=date&size=100 [Last accessed on
Writing – original draft: Lip-Yuen Teng 2024 May 28].
Writing – review & editing: All authors 10. Vignot S, Faivre S, Aguirre D, Raymond E. mTOR-targeted
therapy of cancer with rapamycin derivatives. Ann Oncol.
Ethics approval and consent to participate 2005;16(4):525-537.
Not applicable. doi: 10.1093/annonc/mdi113
Consent for publication 11. Sabatini DM, Erdjument-Bromage H, Lui M, Tempst P,
Snyder SH. RAFT1: A mammalian protein that binds
Not applicable. to FKBP12 in a rapamycin-dependent fashion and is
homologous to yeast TORs. Cell. 1994;78(1):35-43.
Availability of data
doi: 10.1016/0092-8674(94)90570-3
Not applicable.
12. Laplante M, Sabatini DM. mTOR signaling in growth
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Volume 3 Issue 3 (2024) 16 doi: 10.36922/an.3568