IHC 2021 | Treating migraine: indirect glutamate modulation
Anna Andreou, PhD, King’s College London, London, UK, discusses indirect strategies to block glutamate activation to treat migraine. Glutamate is the major neurotransmitter in the brain, so blocking its activation could lead to significant adverse events. As a strategy to avoid such complications, research has turned its focus to indirect glutamate modulation. One of the indirect strategies currently under investigation is the use of kynurenic acid analogs. Kynurenic acid is known to have a binding site on the NMDA receptor, and studies have reported kynurenic acid and metabolites on the plasma of migraine patients during an attack. Additionally, preclinical studies have shown that kynurenic acid analogs can be effective modulators of trigeminal activation. Other strategies include the novel development of recombinant botulinum toxin, a well-established preventive migraine treatment. Novel botulinum toxin molecules that can have specific targets have been developed. Potentially, a novel botulinum toxin could be designed to target the glutamate transporters and specifically block glutamatergic transmission from the peripheral branch of the trigeminal nerve. This interview took place during the International Headache Congress 2021.
Transcript (edited for clarity)
There are ways we can target the glutamatergic system indirectly, rather than directly blocking the glutamate receptors, which as we said, will have considerable side effects. One way, for example, is through the kynurenic acid, which has been known to have a binding site on the NMDA receptor. Also, studies have shown that kynurenic acid and metabolites are found in the plasma of migraine patients during an attack, hence using kynurenic acid analogs, a lot of preclinical studies have shown that it can be an effective modulators...
There are ways we can target the glutamatergic system indirectly, rather than directly blocking the glutamate receptors, which as we said, will have considerable side effects. One way, for example, is through the kynurenic acid, which has been known to have a binding site on the NMDA receptor. Also, studies have shown that kynurenic acid and metabolites are found in the plasma of migraine patients during an attack, hence using kynurenic acid analogs, a lot of preclinical studies have shown that it can be an effective modulators. They can be effective modulators of the trigeminal activation, hence this can be one of the indirect strategies to modulate glutamatergic transmission in the future.
Another way, it could be with the novel development of recombinant botulinum toxin, as you know, Botox, botulinum toxin is a well-established preventive treatment for migraine. And these days biochemical engineering has been evolutionary in terms of synthesizing novel botulinum toxin molecules that can have specific targets. So potentially, such a novel botulinum toxin could be designed to specifically target the vesicular glutamate transporters, hence it will specifically block glutamatergic transmission from the peripheral branch of the trigeminal nerve.
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Disclosures
Honoraria for educational purposes from AbbVie, Allergan, Eli Lilly, eNeura, Zenith Scientific.
Honoraria for advisory purposes from Allergan, Eli Lilly, eNeura, Neuresta, Zenith Scientific.
R&D funding from eNeura, Eli Lilly.
Sponsorship for educational purposes from Allergan, ATI, Eli Lilly, eNeura, Novartis.
Board member of GSConsulting, Neuresta.
