Intracerebroventricular administration for delivery of antiseizure therapeutics: Challenges and opportunities

Firas Fahoum*, Sara Eyal*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

Intracerebroventricular (ICV) administration is increasingly being explored as a means for delivering antiseizure and antiepileptic therapies to epileptic brain tissue. This route bypasses the blood–brain barrier, thus enabling the delivery of therapeutics that are restricted from the brain, while reducing the risk of systemic adverse reactions. Nevertheless, projections from studies in patients with other diseases suggest that efficacy of some ICV-delivered therapeutics may be limited when the epileptogenic tissue or network circuits are localized more than a few millimeters away from the ventricles. In this article, we present the characteristics of the cerebrospinal fluid as a drug administration site, the brain barriers, and their relevance to treating focal and generalized epilepsies. We refer to ICV delivery of advanced therapies for treating neurodevelopmental disorders with epilepsy. We describe properties of therapeutic compounds, from small molecules to RNA-based therapeutics, proteins, and viral vectors, which can make them either fitting or poor candidates for ICV administration in epilepsy. We additionally provide an overview of preclinical studies and clinical trials involving the ICV route of delivery. Finally, we compare ICV delivery with other routes of administration that bypass the cerebral circulation. This review aims to provide information that will hopefully help investigators select candidate patients and therapeutics for ICV therapies, and to highlight advantages and challenges inherent to this approach.

Original languageEnglish
Pages (from-to)1750-1765
Number of pages16
JournalEpilepsia
Volume64
Issue number7
DOIs
StatePublished - Jul 2023

Keywords

  • CSF–brain barrier
  • antiepileptic drugs
  • blood–brain barrier
  • cerebrospinal fluid
  • drug delivery
  • epilepsy
  • epileptic networks
  • seizures
  • temporal lobe epilepsy

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