2. Academic Validation
  3. Preventing neuropathy and improving anticancer chemotherapy with a carbazole-based compound

Preventing neuropathy and improving anticancer chemotherapy with a carbazole-based compound

  • Sci Adv. 2025 Oct 31;11(44):eadw6328. doi: 10.1126/sciadv.adw6328.
Lauriane Bosc 1,  Maria Elena Pero 2 3,  David Balayssac 4,  Nathalie Jacquemot 5,  Jordan Allard 1,  Peggy Suzanne 6,  Julien Vollaire 1,  Cécile Cottet-Rousselle 7,  Sophie Michallet 1,  Joran Villaret 1,  Sakina Torch 1,  Sumari Marais 8,  Bénédicte Elena-Herrmann 1,  Uwe Schlattner 7 9,  Anne Mercier 8,  Véronique Josserand 1,  Chantal Thibert 1,  Patrick Dallemagne 6,  Francesca Bartolini 2,  Laurence Lafanechère 1 8
Affiliations

Affiliations

  • 1 Université Grenoble Alpes, INSERM U1209, CNRS UMR 5309, Institute for Advanced Biosciences (IAB), 38000 Grenoble, France.
  • 2 Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
  • 3 Department of Veterinary Medicine and Animal Production, University of Naples Federico II, 80137 Naples, Italy.
  • 4 Université Clermont Auvergne, U1107, NEURO-DOL, INSERM, CHU Clermont-Ferrand, Direction de la Recherche Clinique et de l'Innovation, Clermont-Ferrand, France.
  • 5 Université Clermont Auvergne, U1107, NEURO-DOL, INSERM, Clermont-Ferrand, France.
  • 6 Université Normandie, UNICAEN, CERMN, 14032 Caen, France.
  • 7 Laboratory of Fundamental and Applied Bioenergetics, Université Grenoble Alpes, INSERM U1055, Grenoble, France.
  • 8 Department of Physiology, School of Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria 0028, South Africa.
  • 9 Institut Universitaire de France (IUF), 75231 Paris, France.
PMID: 41160692 DOI: 10.1126/sciadv.adw6328
Abstract

While advances in Cancer therapy have improved remission rates, chemotherapy-induced peripheral neuropathy (CIPN) remains a lasting and untreatable side effect. This study introduces Carba1, a bifunctional carbazole compound that protects against CIPN through two mechanisms. First, Carba1 interacts with tubulin, allowing for lower doses of taxanes, common chemotherapeutics known for causing CIPN, without reducing their Anticancer effectiveness. Second, Carba1 activates nicotinamide phosphoribosyltransferase (NAMPT), enhancing NAD biosynthesis and boosting the metabolic resilience of neurons and Schwann cells against chemotherapy-induced damage. Carba1 shows strong neuroprotective effects in vitro against paclitaxel, cisplatin, and bortezomib toxicity and in vivo in a rat model of paclitaxel-induced neuropathy. Crucially, Carba1 does not interfere with paclitaxel's tumor-fighting ability or promote tumor growth. Structure-activity analyses of Carba1 derivatives reveal the potential to develop compounds with dual or solely neuroprotective effects. These findings position Carba1 as a promising candidate to prevent CIPN, with potential to enhance both Cancer treatment outcomes and patients' quality of life.

Figures
Products