Transcranial Magnetic Stimulation Enhances the Therapeutic Effect of IGF-Trap in Intracerebral Glioma Models

Background: Glioblastoma multiforme is an aggressive malignancy with a dismal 5-year survival rate of 5-10%. Current therapeutic options are limited, due in part to drug exclusion by the blood-brain barrier (BBB). We have previously shown that high-amplitude repetitive transcranial magnetic stimulation (rTMS) in rats allowed the delivery across the BBB of an IGF signaling inhibitor-IGF-Trap. The objective of this study was to assess the therapeutic effect of IGF-Trap when delivered in conjunction with rTMS on the intracerebral growth of glioma. Results: We found that systemic administration of IGF-Trap without rTMS had a minimal effect on the growth of orthotopically injected glioma cells in rats and mice, compared to control animals injected with vehicle only or treated with sham rTMS. In rats treated with a combination of rTMS and IGF-Trap, we observed a growth retardation of C6 tumors for up to 14 days post-tumor cell injection, although tumors eventually progressed. In mice, tumors were detectable in all control groups by 14-17 days post-injection of glioma GL261 cells and progressed rapidly thereafter. In mice treated with rTMS prior to IGF-Trap administration, tumor growth was inhibited or delayed, although the tumors also eventually progressed. Conclusion: The results showed that rTMS could increase the anti-tumor effect of IGF-Trap during the early phases of tumor growth. Further optimization of the rTMS protocol is required to improve survival outcomes.