High levels of polyamines are found in many human cancers including neuroblastoma. Polyamines can also enhance neuronal sensitization, including development of allodynia and other forms of pathological pain. Anti-GD2 therapy with dinutuximab is effective in improving the survival of high-risk neuroblastoma patients in remission and after relapse. However, allodynia hinders its expanded usage at higher doses. We have developed a rat model where rats injected with 14G2a show paw withdrawal responses to stimuli that mimic allodynia, which is significantly attenuated when rats are allowed to drink water containing DFMO. These results show that polyamine depletion by DFMO is an effective agent for reducing anti-GD2-induced allodynia and may allow dose escalation for neuroblastoma patients and a sufficient reduction in pain that would allow new patient populations to benefit from this therapy.
Figure 1: Schematic of DFMO and polyamines in pain pathways;
Figure 2: After drinking water containing DFMO, rats show a decreased pain response, as measured by paw withdrawal threshold; PLoS One. 2020 Jul 22;15(7):e0236115