For people who face frequent needle jabs to treat chronic conditions, a new technology is on the horizon that might make treatment a lot less painful.
Researchers report that a new wirelessly controlled microchip, implanted under the skin, can safely and reliably give osteoporosis patients the daily dose of a drug that they need for at least 20 days in a row. The findings were presented at the American Association for the Advancement of Science annual meeting in Vancouver and published online Thursday in Science Translational Medicine.
Some 55,000 people in the U.S. with osteoporosis face daily injections of a bone-boosting hormone (known as human parathyroid hormone fragment, which is the basis for the drug teriparatide, sold as Forteo). But during a two-year daily regimen of the shots, close to three quarters of osteoporosis patients fail to take the drug as often as they are supposed to. High noncompliance makes this condition an especially compelling target for an automatic drug-dosing system.
"In a silent disease like osteoporosis, [patients] don't feel any difference, and they just give up the injections all together," says Robert Farra, co-author of the study and chief operating officer at MicroCHIPS, the company that makes the chip. Doctors can either preprogram the new device for a release schedule or send release instructions directly to it via a dedicated radio frequency.
For the study, eight postmenopausal women with osteoporosis had the chip—which is about three by five centimeters and can be implanted during an office visit—inserted under the skin around their bellies for about three and a half months. Daily doses of teriparatide were preprogrammed to release for about 20 days during the middle of the trial. Seven of the eight received most of their doses right on schedule, and each of these said they would opt in for another chip—most reported that they had forgotten that it was there.
Microchips like these could also be used for other conditions that demand discrete drug dosing, such as multiple sclerosis, for which some patients must inject a dose of interferon once every two days. Therapies that use hormones are particularly appealing for adaptation to microchip delivery because the body usually releases hormones intermittently—just as the chip does, Farra says. In the future, a device like this might also be able to help diabetics both monitor and treat their condition.
This sort of direct communication in an implanted device could help patients stick to medication regimes without having to face a syringe or pill bottle.
The device can be preprogrammed or controlled wirelessly via the Medical Implant Communication Services (MICS) band, set aside for the U.S. Food and Drug Administration (FDA) by the Federal Communications Commission. And the device can also report back dose-delivery data to a computer-based system.
Scientists demonstrated that this sort of wirelessly controlled drug delivery might be possible in 1999. Some major technological hurdles needed to be cleared in the interim, Farra says.
The first challenge was figuring out how to create seals on the drug-holding wells that would stand up to moisture inside the body. Researchers solved this by using compression welding to create a hermetic seal around the well's metallic membrane. The second hurdle was figuring out how best to open those tight seals. The scientists settled on an electrical current that would melt the membrane on command. The final hurdle involved scaling things down—getting all the components and wells onto a chip that would fit comfortably under the skin.
Other implantable devices can become bogged down by tissue that grows around them. But the researchers found that even with the extra layer of tissue around it, drug absorption via the chip seemed to work just fine.
The researchers also found that dosing accuracy was actually better than standard injection, says Robert Langer who, with fellow study co-author Michael Cima, both of the Massachusetts Institute of Technology, first started developing the concept of an implantable wireless microchip in the 1990s. And it might not end up being that much more expensive, Farra says.
Farra's group aims to provide the medication-filled chip for a price that will still cost no more, including implant and removal surgery, than the $10,000 to $12,000 that a year's worth of teriparatide injections currently cost. The approach also vastly increases compliance. The current small study did not measure whether or not women with the implant had fewer bone breaks than people who were in charge of their injections. But if future studies find that by increasing compliance patients with the chip also decrease their risk of breaking a bone, then it could also help decrease medical care costs in the long run. With an aging population, the cost of osteoporotic fractures is estimated to top $20 billion by 2015 in the U.S. alone.
External approval for internal dosing
The device still needs perfecting. The eighth patient in the study had a malfunctioning chip that did not release any medication, which might lead some to worry about potential for accidental release of excessive dosages. But with the design of each well's membrane and activation mechanism, Langer says, "I don't think there are big safety concerns."
Other wireless medical devices have raised eyebrows for their potential susceptibility to signal interference or even hacking. Because the device uses the MICS frequency, it is likely to face less interference than if it were on busier parts of the band. Also, a unique ID number is required to establish connection with each individual chip, decreasing the ease of hacking.
Farra and his colleagues have built an implant—the same size as the one in the study—that contains 365 doses, which, they suggest, could provide daily dosing for a year or possibly even every-other-day doses for two years.
Farra suggests that more development and trials could yield a yearlong chip ready for FDA approval in four years.
John Watson, a professor of bioengineering at the University of California, San Diego, thinks this estimate is a tad optimistic. He has been helping to find ways to move technology from the drawing board to clinical use more quickly. But, he says, for a device like this, researchers will need to tweak the technology, recruit more patients, run a one- or two-year-long study and complete another year or two of follow-up—plus time to review the data and seek approval from the FDA. "That's very doable," says Watson, who wrote an editorial about the new device that was also published online Thursday in Science Translational Medicine. It is just a matter of doing it, he says.
If the chip proves successful in larger and longer trials, it might also be adapted for treating more acute conditions, such as delivering drugs for a month or two after a heart attack. The chip could also be filled with a mix of drugs delved out in dosages specifically tailored to a patient's needs, Farra notes. For instance, if a patient is responding well to medication, a doctor could dial back the release frequency. Or if a patient needs to be slowly weaned off or onto a drug, there could be smaller doses preset in the chip.
Farra and his team are working to create a future where this dosing device will also keep tabs on patients. They are turning the chip into a closed-loop system that monitors and treats conditions on its own. They have already developed a sensor that can take glucose readings: If it sensed a drastic change in levels, it could release a tailored dose. Animal trials suggest that these sensors could last for a year or so before they stop working, which is longer than many other current devices being tested. For a high-risk heart failure patient, Farra says, it might be possible for the device to monitor the heart for signs of a heart attack and release drugs to decrease damage to the heart muscle during a cardiac event.
The microchip might not be perfect for every medication. As Langer notes, high-dose drugs, such as antibiotics, probably are better administered in other ways.
Langer sees implantable drug chips as more than just a new tool for doctors and patients—they are a sign that the true "dawn of telemedicine" has arrived, he says. Remote communication with doctors and patients or remote robotic surgery might only have been a warm-up. "You can now do remote control from outside the body," Langer says.