Reducing Brain Edema Using Berotralstat, an Inhibitor of Bradykinin, Repurposed as Treatment Adjunct in Glioblastoma
Glioblastomas synthesize, bear receptors for, and respond to bradykinin, triggering migration and proliferation. Since centrifugal migration into uninvolved surrounding brain tissue occurs early in the course of glioblastoma, this attribute defeats local treatment attempts and is the primary reason...
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MDPI AG
2024-07-01
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| Series: | Neuroglia |
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| Online Access: | https://www.mdpi.com/2571-6980/5/3/16 |
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| author | Richard E. Kast |
| author_facet | Richard E. Kast |
| author_sort | Richard E. Kast |
| collection | DOAJ |
| description | Glioblastomas synthesize, bear receptors for, and respond to bradykinin, triggering migration and proliferation. Since centrifugal migration into uninvolved surrounding brain tissue occurs early in the course of glioblastoma, this attribute defeats local treatment attempts and is the primary reason current treatments almost always fail. Stopping bradykinin-triggered migration would be a step closer to control of this disease. The recent approval and marketing of an oral plasma kallikrein inhibitor, berotralstat (Orladeyo™), and pending FDA approval of a similar drug, sebetralstat, now offers a potential method for reducing local bradykinin production at sites of bradykinin-mediated glioblastoma migration. Both drugs are approved for treating hereditary angioedema. They are ideal for repurposing as a treatment adjunct in glioblastoma. Furthermore, it has been established that peritumoral edema, a common problem during the clinical course of glioblastoma, is generated in large part by locally produced bradykinin via kallikrein action. Both brain edema and the consequent use of corticosteroids both shorten survival in glioblastoma. Therefore, by (i) migration inhibition, (ii) growth inhibition, (iii) edema reduction, and (iv) the potential for less use of corticosteroids, berotralstat may be of service in treatment of glioblastoma, slowing disease progression. This paper recounts the details and past research on bradykinin in glioblastoma and the rationale of treating it with berotralstat. |
| format | Article |
| id | doaj-art-8536adef598e4941a4d8c2215dc6bfb0 |
| institution | OA Journals |
| issn | 2571-6980 |
| language | English |
| publishDate | 2024-07-01 |
| publisher | MDPI AG |
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| series | Neuroglia |
| spelling | doaj-art-8536adef598e4941a4d8c2215dc6bfb02025-08-20T01:55:45ZengMDPI AGNeuroglia2571-69802024-07-015322323310.3390/neuroglia5030016Reducing Brain Edema Using Berotralstat, an Inhibitor of Bradykinin, Repurposed as Treatment Adjunct in GlioblastomaRichard E. Kast0IIAIGC Study Center, 11 Arlington Ct, Burlington, VT 05408, USAGlioblastomas synthesize, bear receptors for, and respond to bradykinin, triggering migration and proliferation. Since centrifugal migration into uninvolved surrounding brain tissue occurs early in the course of glioblastoma, this attribute defeats local treatment attempts and is the primary reason current treatments almost always fail. Stopping bradykinin-triggered migration would be a step closer to control of this disease. The recent approval and marketing of an oral plasma kallikrein inhibitor, berotralstat (Orladeyo™), and pending FDA approval of a similar drug, sebetralstat, now offers a potential method for reducing local bradykinin production at sites of bradykinin-mediated glioblastoma migration. Both drugs are approved for treating hereditary angioedema. They are ideal for repurposing as a treatment adjunct in glioblastoma. Furthermore, it has been established that peritumoral edema, a common problem during the clinical course of glioblastoma, is generated in large part by locally produced bradykinin via kallikrein action. Both brain edema and the consequent use of corticosteroids both shorten survival in glioblastoma. Therefore, by (i) migration inhibition, (ii) growth inhibition, (iii) edema reduction, and (iv) the potential for less use of corticosteroids, berotralstat may be of service in treatment of glioblastoma, slowing disease progression. This paper recounts the details and past research on bradykinin in glioblastoma and the rationale of treating it with berotralstat.https://www.mdpi.com/2571-6980/5/3/16berotralstatblood–brain barrierbradykininC1 esterase inhibitoredemaglioblastoma |
| spellingShingle | Richard E. Kast Reducing Brain Edema Using Berotralstat, an Inhibitor of Bradykinin, Repurposed as Treatment Adjunct in Glioblastoma Neuroglia berotralstat blood–brain barrier bradykinin C1 esterase inhibitor edema glioblastoma |
| title | Reducing Brain Edema Using Berotralstat, an Inhibitor of Bradykinin, Repurposed as Treatment Adjunct in Glioblastoma |
| title_full | Reducing Brain Edema Using Berotralstat, an Inhibitor of Bradykinin, Repurposed as Treatment Adjunct in Glioblastoma |
| title_fullStr | Reducing Brain Edema Using Berotralstat, an Inhibitor of Bradykinin, Repurposed as Treatment Adjunct in Glioblastoma |
| title_full_unstemmed | Reducing Brain Edema Using Berotralstat, an Inhibitor of Bradykinin, Repurposed as Treatment Adjunct in Glioblastoma |
| title_short | Reducing Brain Edema Using Berotralstat, an Inhibitor of Bradykinin, Repurposed as Treatment Adjunct in Glioblastoma |
| title_sort | reducing brain edema using berotralstat an inhibitor of bradykinin repurposed as treatment adjunct in glioblastoma |
| topic | berotralstat blood–brain barrier bradykinin C1 esterase inhibitor edema glioblastoma |
| url | https://www.mdpi.com/2571-6980/5/3/16 |
| work_keys_str_mv | AT richardekast reducingbrainedemausingberotralstataninhibitorofbradykininrepurposedastreatmentadjunctinglioblastoma |