Deferoxamine Improves Radiation-Induced Peripheral Neuropathy

Radiation-induced peripheral neuropathy (RIPN) is a devastating sequela of radiation therapy (XRT). Current treatment options are limited. Deferoxamine (DFO) has been useful in treating radiation-induced dermal fibrosis. This study aimed to evaluate DFO for RIPN. Thus, 18 mice received 30Gy of fractionated XRT. After a fibrosis development interval, mice were treated with DFO injections, saline injections (Saline) or none (IR) (n = 6 per group). Longitudinal measures included footprint analysis, cold allodynia testing and monofilament testing. Immunofluorescent staining for myelination (MPZ) and axonal regeneration (GAP43) took place at the conclusion of the experiment. DFO improved motor deficits (Combined Toe Spread scores: -9.72, -12.91, -12.72 for DFO, Saline and IR, respectively). Additionally, DFO improved cold allodynia (duration ratios: 0.90, 0.70 and 0.73 for DFO, Saline and IR, respectively). Monofilament testing revealed the same trend, though not statistically significant. Additionally, DFO increased remyelination on MPZ staining (normalized myelin ratios: 0.84 DFO, 0.74 Saline, 0.72 IR) and increased axonal regeneration on GAP43 staining compared to all groups (pixel area: 3.76% DFO, 1.95% Saline, 1.94% IR, 2.09% Control). In conclusion, this murine study revealed DFO improves RIPN sensorimotor function. This is encouraging as disease-modifying treatments are limited for patients suffering from this XRT side effect.