Focused Ultrasound andโ Microbubbles Show Promise in Delivering Chemotherapy to Childhood Brain Tumors
researchers have demonstrated the feasibility of using focused ultrasound (FUS) in combination withโ microbubbles to temporarily open the blood-brain โbarrier (BBB) and deliver the chemotherapy drug panobinostat to children with relapsed diffuse midline gliomas (DMGs), โคa especiallyโ aggressive type of brain tumor. โคThe study, published in Science Translational Medicine, represents a โpotential โคstep forward in treating โthis currently incurable disease.
DMGs, often arising in the brainstem, thalamus, โขor spinal cord, are characterized by a specific genetic mutation (H3K27M)โ and have a dismal prognosis, with a median overall survival of just one year. Current treatment options are limited to radiotherapy, and surgery isโฃ frequently enough impractical due toโข the tumors’ location and diffuse nature. A majorโข challenge in treating these โขtumors is the BBB, which effectively shields the brain from many therapies.
The research team, led by Cheng-Chia Wu, PhD,โ from Columbia University, utilized FUS to โexcite microscopic bubbles injected into the bloodstream. This caused the bubbles to expand and contract,gently and temporarily increasing the permeability of the BBB,allowing panobinostat – a histone deacetylaseโ inhibitor showing promise in vitro – to reach the tumor.
Prior studies inโ mouse models had indicated a synergistic effect between FUS and panobinostat. Building on this, the researchers conducted a first-in-pediatric clinical trial involving three children with relapsed DMGs.The FUS treatment wasโ deliveredโค using a mobile ultra-Nav FUS device, allowing for outpatient administration of oral panobinostat every other day.
The study successfully openedโฃ the BBB, as confirmed by magnetic resonance imaging, with โคtreatments โdelivered as frequently as every two days. A total of 22 FUS proceduresโฃ were performed โคtargeting single tumor sites, and four procedures โtargeted two sites. Importantly,โข the procedures were conducted without โsedation or anesthesia forโค the initial single-site treatments.
While treatment โat a single โtumor siteโ was well-tolerated, extending treatment to two sites resulted in prolonged BBB opening and one seriousโค adverse event (grade five), though researchers believe this event was unlikely toโ be directly related to the FUS procedure.โข
The researchers conclude that neuronavigation-guided FUS (NgFUS) mediated BBB opening is a feasible outpatient procedure for children with progressive DIPGs/DMGs, pavingโข the way for further inquiry of combinatorial treatment approaches to improve โคoutcomes for these patients. The findings also address a gap in knowledge regarding the feasibilityโข of frequentโค ultrasound application in children using portable devices.
