Thursday 26 September 2019

Repurposing perampanel (glutamate receptor blocker)?

About a week ago there was a major study published in the journal Nature called "Glutamatergic synaptic input to glioma cells drives brain tumour progression".

https://www.ncbi.nlm.nih.gov/pubmed/31534219

I've uploaded the full study to the Pathology folder in the Brain Tumor Library.

The study discovers a communication network between neurons and glioma cells, with certain effects (including tumor invasiveness) mediated by AMPA type glutamate receptors. Furthermore, these effects were blocked in vitro by the approved AMPA glutamate receptor antagonists, perampanel.

Perampanel was approved in 2012 for  partial seizures and generalized tonic-clonic seizures for people older than 12 years, so could also have anti-seizure effects in addition to potential anti-tumor effects.

The relevant discussion from the Nature paper is as follows:
The selective non-competitive AMPAR antagonist perampanel is an approved antiepileptic drug shown to have potential antitumour effects in patients with glioma and warrants further investigation. Chronic administration of perampanel to xenografted mice decreased the proliferation of GB cells as determined by in vivo imaging of tumour regions over time (Fig. 5j, k, Extended Data Fig. 9a) independently of cell-autonomous effects as determined by an in vitro proliferation assay (Extended Data Fig. 9b).

This is not the first paper to discuss perampanel effects on glioma and/or seizure control for glioma patients. For example:

AMPA receptor antagonist perampanel affects glioblastoma cell growth and glutamate release in vitro
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0211644

Adjunctive perampanel for glioma-associated epilepsy.
https://www.ncbi.nlm.nih.gov/pubmed/30377587

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