Scientists have developed a noninvasive way of delivering drugs to within a few millimeters of a desired point in the brain. The method, described today in a paper published in Neuron, uses focused ultrasound to jiggle drug molecules loose from nanoparticle "cages" that have been injected into the bloodstream.
In a proof-of-principle study, the researchers showed that pharmacologically active amounts of a fast-acting drug could be released from these cages in small areas of the rats' brains targeted by a beam of focused ultrasound. The drug went to work immediately, reducing neural activity in the targeted area—but only while the ultrasound device was active and only where the ultrasound intensity exceeded a certain threshold. By modifying the strength and duration of the beam, the investigators could fine-tune the neural inhibition.
A kindred technology known as optogenetics uses invasive gene delivery to render specified classes of nerve cells vulnerable to precise experimental manipulation. The authors' approach employs noninvasive pharmacological methods to achieve similar control of neural activity.
According to senior author Raag Airan of Stanford University, the new technology could both speed advances in neuroscientific research and move rapidly into clinical practice. "While this study was done in rats, each component of our nanoparticle complex has been approved for at least investigational human use by the Food and Drug Administration, and focused ultrasound is commonly employed in clinical procedures at Stanford," he says. "So, we're optimistic about this procedure's translational potential."
In addition to allowing for targeted drug delivery in the clinic, this new technology could also be useful to aid in brain surgery. "We hope to use this technology to noninvasively predict the results of excising or inactivating a particular small volume of brain tissue in patients slated for neurosurgery," says Airan. "Will inactivating or removing that small piece of tissue achieve the desired effect—for example, stopping epileptic seizure activity? Will it cause any unexpected side effects?"
Karl Deisseroth, pioneer of optogenetics, who wasn't involved in the study, adds, "This important work establishes that ultrasonic drug uncaging appears to have the required precision to tune the brain's activity via targeted drug application. The powerful new technique could be used to test optogenetically inspired ideas, derived initially from rodent studies, in large animals—and perhaps soon in clinical trials."