Rapid Fire 9th Venoms to Drugs 2026

Investigating the Role of Kv1.3 as a Therapeutic Target in Vincristine-Induced Peripheral Neuropathy (#018)

Paula Manuela Rojas Zambrano 1 , Hana Starobova 1 , Svetlana Shatunova 1 , Jennifer Deuis 1 , Ray Norton 2 , Irina Vetter 1 3
  1. Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia
  2. Monash Institute of Pharmaceutical Sciences, University of Melbourne, Melbourne, VIC, Australia
  3. School of Pharmacy, The University of Queensland, Brisbane, QLD, Australia

Vincristine-induced peripheral neuropathy (VIPN) is a common and debilitating complication of chemotherapy, particularly in paediatric and haematological malignancies. Current treatments are largely symptomatic and fail to address the underlying neuroimmune mechanisms that contribute to chronic pain. Increasing evidence implicates macrophage activation, cytokine release, and neuroinflammation within the dorsal root ganglia (DRG) as key drivers of VIPN pathogenesis [1,2].

Kv1.3, a voltage-gated potassium channel expressed in activated immune cells, regulates calcium signalling and pro-inflammatory cytokine production. Its upregulation in neuroinflammatory conditions makes it a compelling therapeutic target for immune-driven neuropathies such as VIPN [3]. HsTX1[R14A], a selective Kv1.3 inhibitor, has demonstrated immunomodulatory efficacy in preclinical models of inflammatory disease [4].

Preliminary findings indicate that Kv1.3 inhibition attenuates vincristine-induced mechanical hypersensitivity and reduces inflammatory responses associated with macrophage activation. Increased Kv1.3 expression was observed under inflammatory conditions, while pharmacological inhibition of Kv1.3 reduced the release of the pro-inflammatory cytokine IL-1β.

These findings support a role for Kv1.3-mediated neuroimmune signalling in VIPN and highlight selective Kv1.3 inhibition as a promising therapeutic strategy for chemotherapy-induced neuropathic pain. Ongoing studies aim to further characterise the mechanisms underlying these effects and evaluate the translational potential of Kv1.3-targeted therapies.

  1. Starobova, H. and I. Vetter, Pathophysiology of Chemotherapy-Induced Peripheral Neuropathy. Front Mol Neurosci, 2017. 10: p. 174.
  2. Starobova, H., et al., Vincristine-induced peripheral neuropathy is driven by canonical NLRP3 activation and IL-1β release. Journal of Experimental Medicine, 2021. 218(5).
  3. Beeton, C., et al., Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases. Proc Natl Acad Sci U S A, 2006. 103(46): p. 17414-9.
  4. Rashid, M.H., et al., A potent and Kv1.3-selective analogue of the scorpion toxin HsTX1 as a potential therapeutic for autoimmune diseases. Sci Rep, 2014. 4: p. 4509.