Recurrent Glioblastoma Multiforme (rGBM) of Drug Development
Glioblastoma multiforme (GBM) patients face a dismal prognosis, with recurrence virtually inevitable. RGBM has no currently effective means of treatment.
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Currently, there are devices being assessed in GBM clinical trials for their ability to open the blood brain barrier and improve chemotherapeutic drug delivery. This approach may be challenging because 80-90% of GBMs recur after excision within 2-4 cm (~1 to 1.5 inch) of the visible tumor resection border, in the area of normal-appearing brain. Therefore, effective therapy would require a chemotherapeutic agent selective only for GBM cells. There is no such chemotherapeutic agent yet available.
Unlike the approaches outlined above, ALA is selectively taken up by GBM cells where it is converted to protoporphyrin. MRGFUS activates protoporphyrin to create reactive oxygen species that kill tumor cells immediately and simultaneously trigger programmed cell death (apoptosis). ALA + MRGFUS together create a therapeutic noninvasive process called ALA sonodynamic therapy (SDT). Both ALA and the MRGFUS device are individually FDA-approved for other intracranial indications and have been shown to be safe and well-tolerated for those indications.
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