By David Warmflash
While patient-controlled drug delivery is already common, particularly in the context of pain management (patient controlled analgesia [PCA]), new research hints that patient control might eventually go far beyond controlling the infusion by hand. How much farther? How about commanding a new bolus with a thought, or even mentally controlling the amount that comes in?
Of course, as with current technology, controlling the amount would mean within physician-ordered parameters. So, we’re imaging a kind of PCA 2.0, although it might do more than just analgesia. Being able to command drug delivery with the mind could be useful in virtually any situation in which the patient’s sense of medication need is good.
The idea comes from a recent study published in Nature that combined two technologies—optogenetics and neuroelectromechanical interfaces—to achieve human mind control of gene expression. Using cell culture and a mouse model for optogenetic expression of the well-studied enzyme secreted alkaline phosphatase (SEAP), a team of Swiss and French researchers found that human subjects could learn to not only to turn the gene on and off, but even to regulate its expression. Optogenetics involves the utilization of genes for proteins that respond to light. In nature, there are a variety of such proteins, varying in terms of the range of wavelengths of light that affect them. With genetic engineering techniques, these genes can be moved between species and used as switches to control the expression of other genes, such as SEAP. In this case, the researchers chose an optogenetic system responsive to near infrared (NIR) light, because NIR penetrates tissues, such as skin.
The tissue penetrating ability allowed for use of a wireless implant able to release SEAP into the bloodstream of test mice when stimulated by NIR light. Additionally, the implant could be tested in cell cultures, where the amount of gene product released could be measured prior to animal testing.
With the optogenetic system in place and responsive to NIR light, the trick then was to use human thought to control the light. Inspired by a Mattel toy called Mindflex that uses a simple electroencephalographic interface on a Blue-tooth-like headset to steer a ball through an obstacle course, the researchers developed a similar mechanism. In this system, human subjects learned to put themselves into three possible states of mind: biofeedback control, concentration, and meditation. EEG signals were used to control on-off switching of an NIR light in the implant, which housed the optogenetic cells that released the SEAP gene in response to the light. After some practice, the subjects were able to turn SEAP secretion on and off at will and even regulate it.
Using pain management as the example, future systems using the technology might be developed to stimulate synthesis of gene product like beta-endorphin. Beyond that, the authors of the Nature study imagine using EEG patterns linked to optogenetic machines to control devices such as insulin pumps, cochlear implants and other bionic devices, even heart implants. With the marriage of two such powerful technologies, the potential for drug delivery seems limitless.