Past, present and future of Focused Ultrasound as an adjunct or complement to DIPG/DMG therapy: A consensus of the 2021 FUSF DIPG meeting.

Diffuse Intrinsic Pontine Glioma (DIPG), now known as Diffuse Midline Glioma (DMG) is a devastating pediatric brain tumor with limited treatment options and a very poor prognosis. Despite more than 250 clinical trials aimed to treat children diagnosed with DMG, no curative therapies currently exist for this patient population. A major obstacle has been the intact blood brain barrier (BBB) which prevents most therapeutics from crossing into the tumor bed. Focused Ultrasound (FUS) is an emerging, noninvasive medical technology which has been shown in both preclinical and clinical research to disrupt the blood brain barrier safely and temporarily. FUS blood brain barrier opening has been studied in combination with chemotherapies in preclinical DMG models, and this technology is now being investigated in clinical trials for the treatment of pediatric brain tumors. Focused ultrasound has additional mechanisms of action, including sonodynamic therapy and radiation sensitization, that hold promise as future DMG therapies as well. This paper, largely based off the proceedings from a workshop held by the Focused Ultrasound Foundation in October of 2021, summarizes the current state of the field of focused ultrasound for DIPG/DMG, including preclinical, technical, and clinical summaries in addition to recommended next steps for continued advancement of the game changing technology of Focused Ultrasound.

Metabolic homeostasis via BDNF and its receptors.

Metabolic disorders result from dysregulation of central nervous system and peripheral metabolic energy homeostatic pathways. To maintain normal energy balance, neural circuits must integrate feedforward and feedback signals from the internal metabolic environment to orchestrate proper food intake and energy expenditure. These signals include conserved meal and adipocyte cues such as glucose and leptin, respectively, in addition to more novel players including brain-derived neurotrophic factor (BDNF). In particular, BDNF's two receptors, tropomyosin related kinase B (TrkB) and p75 neurotrophin receptor (p75NTR), are increasingly appreciated to be involved in whole body energy homeostasis. At times, these two receptors even seem to functionally oppose one another's actions, providing the framework for a potential neurotrophin mediated energy regulatory axis, which we explore further here.