Columbia Engineering researchers have developed a new technique to reach neurons
through the blood-brain barrier (BBB) and deliver drugs safely and
noninvasively. Up until now, scientists have thought that long ultrasound
pulses, which can inflict collateral damage, were required. But in this new
study, the Columbia Engineering team show that extremely short pulses of
ultrasound waves can open the blood-brain barrier – with the added advantages of
safety and uniform molecular delivery – and that the molecule injected
systemically could reach and highlight the targeted neurons noninvasively.
The study, led by Elisa Konofagou, associate professor of biomedical
engineering and radiology, will be published in the online Early Edition of the
Proceedings of the National Academy of Sciences the week of September 19,
2011.
“This is a great step forward,” says Konofagou. “Devastating
diseases such as Alzheimer’s and Parkinson’s that affect millions of people are
currently severely undertreated. We hope our new research will open new avenues
in helping eradicate them.”
Highly specific delivery of drugs to human
organs is essential for the effective treatment of many diseases. But the brain
presents a difficult problem: it has a unique vascular system – the blood-brain
barrier – that acts as a closed door to prevent the entry of foreign molecules.
While it protects the brain from potentially toxic substances, it also prevents
the delivery of therapeutic drugs to the brain. Because many molecules cannot
cross the BBB, available treatments for patients with neurological disorders
have been severely limited. Konofagou and her team are focused on getting the
door opened enough to safely reach those cells that need to be treated.
Konofagou and her team have designed a focused ultrasound method that
can target only the area of the hippocampus that is affected in early
Alzheimer’s. In this study, they administered microbubbles to enhance the
intended mechanical effect, and a high-field MRI to detect and map the area of
BBB opening as well as quantify the permeability of the opened BBB. They also
used fluorescence confocal microscopy to visualize the molecular diffusion and
neuronal enhancement in 3-D to identify both highlighted neurons and their
network.
More testing is planned with therapeutic drug treatments.
Konofagou’s team has shown that therapeutic molecules trigger downstream effects
after diffusion through the blood-brain barrier, starting with the cell membrane
and all the way through the nucleus. They also are unveiling the mechanism of
the opening that involves stable oscillation or collapse of the bubble, with the
former being the preferred mechanism as it is? completely controlled by the
pressure and microbubble size.
The blood-brain barrier has been shown to
recover within the range of three hours to three days depending on the
aforementioned parameters used. Konofagou’s group has also recently reported
that transcranial human targeting of the hippocampus, caudate, and putamen in
the human brain is feasible in both simulations and in vitro experiments, thus
paving the way towards clinical applications.
The Columbia Engineering
study was funded by the National Institutes of Health, the National Science
Foundation, and the Kinetics foundation.
Source: Medical News Today
