Briefly, the authors repeatedly, transiently opened the blood-brain barrier (BBB) of an animal model of AD using scanning ultrasound. They observed that AD-like behavioral and brain symptomology was reduced in the treated animals. They suggest that the effects may be related to potentiating bloodflow to the brain and thereby enhancing clean-up of AD-related pathology.
The challenges going forward are described in their limitations section:
"At this stage, several hurdles have to be faced for SUS to be considered for application in human patients. In addition to the limitation presented by the animal model used in our study, it needs to be considered that the human brain is much larger than that of a mouse. Also, the thicker human skull presents an obstacle that needs to be factored in when parameters are defined that have the envisaged biological effect in the absence of tissue damage. There may also be the necessity to use one of several cranial windows to access the human brain. Also, if one were to apply SUS in humans at the prodromal stage before overt symptoms of AD were present, the safety of this approach would need to be monitored in real time. This could be facilitated by the recent development of advanced methods, such as passive cavitation detection, which is currently being evaluated in both rodents and primates (29). To avoid potentially excessive immune activation in a clinical setting (30), the ultrasound treatment regimen could possibly be done stepwise, covering one brain area at a time.Whereas we only coupled ultrasound with microbubbles, previous studies in rodents evaluated ultrasound for the delivery of therapeutic agents, such as antibodies (31, 32), viral vectors (33), and dextran of different sizes (9, 10). One study targeted Ab using a few entry points for delivery and only a single treatment (34). Because the effect on Ab plaques was very modest, the authors of this study suggested that focused ultrasound would best be suited as a delivery tool, for example, to boost the uptake of peripherally administered anti-Ab antibodies (34). Our results, however, demonstrated that repeated SUS treatment of the entire mouse brain was sufficient to markedly ameliorate the pathology of Ab-depositing mice as analyzed histologically, biochemically, and behaviorally.Our study highlights the potential of SUS treatment as a therapeutic approach for AD and possibly other diseases involving protein aggregation. However, this does not rule out the possibility that it could also be used as a vehicle for drug or gene delivery, given that the BBB remains themajor obstacle for the uptake by brain tissue of therapeutic agents from the circulation (9)."
In summary, it's an interesting approach, but I'm not holding my breath.
Comments
Seems too good to be true. Can someone put this into perspective? Is it promising?
Briefly, the authors repeatedly, transiently opened the blood-brain barrier (BBB) of an animal model of AD using scanning ultrasound. They observed that AD-like behavioral and brain symptomology was reduced in the treated animals. They suggest that the effects may be related to potentiating bloodflow to the brain and thereby enhancing clean-up of AD-related pathology.
The challenges going forward are described in their limitations section:
"At this stage, several hurdles have to be faced for SUS to be considered for application in human patients. In addition to the limitation presented by the animal model used in our study, it needs to be considered that the human brain is much larger than that of a mouse. Also, the thicker human skull presents an obstacle that needs to be factored in when parameters are defined that have the envisaged biological effect in the absence of tissue damage. There may also be the necessity to use one of several cranial windows to access the human brain. Also, if one were to apply SUS in humans at the prodromal stage before overt symptoms of AD were present, the safety of this approach would need to be monitored in real time. This could be facilitated by the recent development of advanced methods, such as passive cavitation detection, which is currently being evaluated in both rodents and primates (29). To avoid potentially excessive immune activation in a clinical setting (30), the ultrasound treatment regimen could possibly be done stepwise, covering one brain area at a time.Whereas we only coupled ultrasound with microbubbles, previous studies in rodents evaluated ultrasound for the delivery of therapeutic agents, such as antibodies (31, 32), viral vectors (33), and dextran of different sizes (9, 10). One study targeted Ab using a few entry points for delivery and only a single treatment (34). Because the effect on Ab plaques was very modest, the authors of this study suggested that focused ultrasound would best be suited as a delivery tool, for example, to boost the uptake of peripherally administered anti-Ab antibodies (34). Our results, however, demonstrated that repeated SUS treatment of the entire mouse brain was sufficient to markedly ameliorate the pathology of Ab-depositing mice as analyzed histologically, biochemically, and behaviorally.Our study highlights the potential of SUS treatment as a therapeutic approach for AD and possibly other diseases involving protein aggregation. However, this does not rule out the possibility that it could also be used as a vehicle for drug or gene delivery, given that the BBB remains themajor obstacle for the uptake by brain tissue of therapeutic agents from the circulation (9)."
In summary, it's an interesting approach, but I'm not holding my breath.