Ultrasound is a pressure wave above the range of human hearing. Ultrasound can obviously be used as an imaging tool at higher frequencies, and at lower frequencies it can be used to deliver energy, for example, into the brain. And we use ultrasound both as a neuromodulatory and as a blood-brain barrier opening tool. In the clinical setting, ultrasound can be used at high frequency. So this is called high-intensity focused ultrasound...
Ultrasound is a pressure wave above the range of human hearing. Ultrasound can obviously be used as an imaging tool at higher frequencies, and at lower frequencies it can be used to deliver energy, for example, into the brain. And we use ultrasound both as a neuromodulatory and as a blood-brain barrier opening tool. In the clinical setting, ultrasound can be used at high frequency. So this is called high-intensity focused ultrasound. For example, to ablate tissue in the thalamus. For example, to treat essential tremor or tremor-dominant Parkinson’s disease. And there, ultrasound is being used as a continuous pressure wave, so there’s a continuous pulse, and thereby in the tissue to which the focus of the ultrasound is being directed, the temperature slowly increases, and it would increase to 55 or 60 degrees, and thereby tissue is coagulated. And this can then be used, for example, to manipulate brain circuits. And therefore, high-intensity focused ultrasound is being used as a treatment modality, for example, to treat essential tremor or tremor-dominant Parkinson’s disease. So we use ultrasound at a low-intensity, also called low-intensity focused ultrasound, and thereby one uses ultrasound as pulsed waves, so not as a continuous wave, and therefore one does not achieve high temperature. Whenever the microbubbles oscillate, this then allows for an increased uptake, up to 20-fold, of the co-delivered therapeutic, for example, an anti-tau antibody. So we use ultrasound as a pressure wave, using ultrasound on its own. We can use ultrasound with microbubbles, which achieves blood-brain barrier opening. And we can use ultrasound with microbubbles and a therapeutic agent, for example, an anti-tau or an anti-amyloid antibody. And we have shown in animal experimentation that there is utility for all three approaches. When we use ultrasound on its own, we can restore cognition in senescent mice and in amyloid-depositing mice. We can use ultrasound with microbubbles and thereby achieve amyloid clearance and restoration of memory functions in amyloid-depositing mice. And, for example, we can use amyloid-depositing mice and co-deliver a therapeutic antibody such as aducanumab, thereby we can achieve a more pronounced amyloid clearance and ensure cognitive improvements.
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