2. Academic Validation
  3. Repurposing of Chemokine Antagonists for Combined Phase-Resolved Spinal Cord Injury Treatment

Repurposing of Chemokine Antagonists for Combined Phase-Resolved Spinal Cord Injury Treatment

  • Adv Sci (Weinh). 2025 Oct 28:e16569. doi: 10.1002/advs.202516569.
Alexey A Belogurov Jr 1 2,  Georgii B Telegin 3,  Aleksandr S Chernov 1 3,  Anna A Kudriaeva 1,  Alexey N Minakov 1 3,  Maksim V Rodionov 4,  Vitaly A Kazakov 3,  Viktor A Palikov 3,  Yuri M Poluektov 5,  Rustam H Ziganshin 1,  Daria A Orlova 1,  Alena S Evpak 1,  Daniil A Barsuk 3,  Fedor A Mesheryakov 1 3,  Aldo Spallone 1 6,  Dmitry S Asyutin 5,  Igor N Pronin 5,  Nikolay A Konovalov 5,  Dmitri Yu Usachev 5,  Alexander G Gabibov 1,  Alexander N Konovalov 5
Affiliations

Affiliations

  • 1 Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia.
  • 2 Department of Biological Chemistry, Russian University of Medicine, Ministry of Health of Russian Federation, Moscow, 127473, Russia.
  • 3 Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, 142290, Russia.
  • 4 Medical Radiological Research Center (MRRC) named after A.F. Tsyb, Branch of the National Medical Radiological Research Center, Ministry of Health of Russian Federation, Obninsk, 249031, Russia.
  • 5 N.N. Burdenko National Scientific and Practical Center for Neurosurgery, Ministry of Health of Russian Federation, Moscow, 125047, Russia.
  • 6 Department of Clinical Neurosciences, NCL-Neuromed Institute of Neurosciences, Rome, 00178, Italy.
PMID: 41147460 DOI: 10.1002/advs.202516569
Abstract

Spinal cord injury (SCI) is a medical challenge that results in the formation of a glial scar preventing recovery of axonal conductivity. Cytokines and chemokines significantly affect the pathogenesis of SCI and represent important targets for therapeutic intervention. Here, dozens of cytokines and chemokines are dynamically monitored in plasma, cerebrospinal fluid, and injury site released in response to experimental SCI conducted in two rodent strains and patients undergoing surgical removal of intramedullary tumors. Dataset comprising 6,172 cytokine/chemokine values across 8 time points suggests that SCI in mammals is accompanied by a massive cytokine storm in cerebrospinal fluid, mainly driven by CXCL1, IL-6, and CCL2-5. Sub-acute phase is mostly associated with IL-2, IL-7, CCL22 and CX3CL1, whereas TNFα and IL17α permanently persists in CNS for even weeks following SCI. The effects of mogamulizumab and chemical antagonists of C-C/C-X-C chemokine receptors TAK-799, SB225002, and MK-7123 on SCI recovery in rodents are further estimated. Here blockade of CCR5 and CXCR1/2 chemokine receptors is shown beneficial for amelioration of acute SCI, whereas anti-CCR4 antibody mogamulizumab readily prevents secondary inflammation in the injured area. Summarizing, the current report claims for a novel combined time-resolved therapeutic modality in SCI treatment, which supports feasibility and motivates off-label clinical evaluation in appropriate cohorts.

Keywords

chemokines; cytokines; mogamulizumab; spinal cord injury; treatment.

Figures
Products