Hydrogen sulfide (H2S), a by-product of cysteine metabolism, inhibits the growth of cultured glioblastoma cells and impairs progression of glioblastoma tumors developing in vivo in laboratory mice. Additionally, endogenous H2S production and signaling via protein sulfhydration are decreased in human glioblastoma brain tissues compared to non-cancerous brain tissue. Thus, boosting H2S levels is a promising and novel therapeutic strategy for treating glioblastoma. The use of exogenous H2S is difficult to translate to the clinic due to toxicity and volatility. Therefore, bolstering endogenous H2S synthesis and signaling represents a safe and promising method to mitigate disease progression. Based on previously published data, which detailed the use of the thyroid hormone inhibitor propylthiouracil (PTU) to enhance endogenous H2S production in mice, and a previous clinical trial at CCF utilizing PTU to increase the survival of glioblastoma patients, revisiting the use of thyroid hormone inhibitors to de-repress endogenous H2S production concurrent with standards of care poses a novel therapeutic avenue. In the nearly two decades since the aforementioned clinical trial, PTU has been largely replaced in clinical endocrinology by the safer and more efficient thyroid inhibitor methimazole. Given our recent success elucidating the importance of tumor suppressive H2S in the realm of GBM, it is hypothesized that reduced thyroid hormone production via oral methimazole intake will bolster the effectiveness of frontline therapy and extend survival by boosting H2S production and function within the tumor-bearing brain. The goal of this trial is to provide proof of the concept that suppression of thyroid hormone signaling via methimazole and subsequent augmentation of H2S synthesis and signaling is feasible in patients with glioblastoma. Achievement of this goal will motivate and guide further therapeutic development of this combinatorial therapeutic approach.
The purpose of this study is to test the effectiveness, safety, and tolerability of a drug called Methimazole. The investigational drug, Methimazole is not FDA approved for brain tumors, but it is used to treat thyroid illnesses. Different doses of Methimazole will be given to several study participants with glioblastoma. The first several study participants will receive the lowest dose. If the drug does not cause serious side effects, it will be given to other study participants at a higher dose. The doses will continue to increase for every group of study participants until the side effects occur that require the dose to be lowered. The procedures in this study are research blood draws, physical exams, collection of medical history, MRI scans, and study drug administration.