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  3. Integrating and optimizing tonabersat in standard glioblastoma therapy: A preclinical study

Integrating and optimizing tonabersat in standard glioblastoma therapy: A preclinical study

  • PLoS One. 2024 Mar 15;19(3):e0300552. doi: 10.1371/journal.pone.0300552.
Velislava Zoteva 1,  Valerie De Meulenaere 1,  Christian Vanhove 2,  Luc Leybaert 3,  Robrecht Raedt 4,  Leen Pieters 5,  Anne Vral 5,  Tom Boterberg 6,  Karel Deblaere 1
Affiliations

Affiliations

  • 1 Department of Radiology, Ghent University, Ghent, Belgium.
  • 2 IBiTech-Medisip-Infinity lab, Ghent University, Ghent, Belgium.
  • 3 Physiology Group, Department of Basic and Applied Medical Sciences, Ghent University, Ghent, Belgium.
  • 4 Department of Head and Skin, Ghent University, Ghent, Belgium.
  • 5 Department of Human Structure and Repair, Ghent University, Ghent, Belgium.
  • 6 Department of Radiation Oncology, Ghent University Hospital, Ghent, Belgium.
PMID: 38489314 DOI: 10.1371/journal.pone.0300552
Abstract

Glioblastoma (GB), a highly aggressive primary brain tumor, presents a poor prognosis despite the current standard therapy, including radiotherapy and temozolomide (TMZ) chemotherapy. Tumor microtubes involving connexin 43 (Cx43) contribute to glioma progression and therapy resistance, suggesting Cx43 inhibition as a potential treatment strategy. This research aims to explore the Adjuvant potential of tonabersat, a Cx43 gap junction modulator and blood-brain barrier-penetrating compound, in combination with the standard of care for GB. In addition, different administration schedules and timings to optimize tonabersat's therapeutic window are investigated. The F98 Fischer rat model will be utilized to investigate tonabersat's impact in a clinically relevant setting, by incorporating fractionated radiotherapy (three fractions of 9 Gy) and TMZ chemotherapy (29 mg/kg). This study will evaluate tonabersat's impact on tumor growth, survival, and treatment response through advanced imaging (CE T1-w MRI) and histological analysis. Results show extended survival in rats receiving tonabersat with standard care, highlighting its Adjuvant potential. Daily tonabersat administration, both preceding and following radiotherapy, emerges as a promising approach for maximizing survival outcomes. The study suggests tonabersat's potential to reduce tumor invasiveness, providing a new avenue for GB treatment. In conclusion, this preclinical investigation highlights tonabersat's potential as an effective Adjuvant treatment for GB, and its established safety profile from clinical trials in migraine treatment presents a promising foundation for further exploration.

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