Thursday, February 16, 2012

Langer spinout MicroCHIPS gets clinical trial

By Lori Valigra

An implantable microchip built using technology spun out of serial entrepreneur Robert Langer’s lab at MIT has been used in a clinical trial to release medicine via a remote-controlled button to women with osteoporosis.

The clinical trial, composed of a group of women with osteoporosis in Denmark, is the first to test a wirelessly controlled microchip that can release drugs into the body at any time instead of using daily injection pens, according to a study in today’s Science Translational Medicine.

“Patients will be freed from having to remember to take their medication and don’t have to experience the pain of multiple injections,” Robert Farra, president and CEO of MicroCHIPS Inc., said in a statement. The Waltham company was spun out of Langer’s lab at MIT in 1999. Farra, Langer, and their colleagues from MIT, Harvard Medical School, OnDemand Therapeutics Inc. and Case Western Reserve University co-authored the study. MicroCHIPS also funded the Danish study.
 
Most drug delivery devices release small amounts of drug slowly over time. By contrast, the microchip can release medication into the bloodstream quickly on command from an external wireless device. Farra said doctors “will be able to seamlessly adjust their patients’ therapy using a computer or cell phone.” The company said it plans to file for regulatory approval for its first microchip device in 2014, and hopes to make it available for mainstream use in five years.

The authors said the microchip may be more appealing and possibly cheaper than long-term use of prefilled daily injection pens. Patients with severe osteoporosis often give themselves daily injections of medication that requires refrigeration. Osteoporosis is a silent disease in which affected individuals don’t feel better or worse as their bone density decreases, so many patients may stop taking medication, the researchers said.
 
The device may also be used to treat other chronic diseases like multiple sclerosis, heart disease, or cancer, the scientists said.
 
The small device - roughly the size of a pacemaker - has 10 individually addressable reservoirs filled with drug solution. The reservoirs pop open either on a pre-programmed schedule or via a wireless signal. The patients had two microchips implanted for a total of 20 doses of drug.
 
“The drugs are in different wells. Each of these wells is covered by a nano-thin layer of gold which protects the drug for years if needed and prevents it from being released,” Langer explained. Sending a wireless signal to the well causes the gold to dissolve, freeing medication into the bloodstream.
 
Adapting microchip technology for human use was a challenge. The microchip was able to deliver drugs in the lab, but once it was implanted into animals, a fibrous collagen-based membrane tended to develop around it. The scientists said they first had to figure out how to seal each reservoir airtight at room temperature. They developed a special compression welding process to provide a long-term seal. The researchers also developed the gold layer, which is strong enough to protect the contents of each reservoir, but thin enough to dissolve on command.
 
The researchers said they were concerned that the fibrous tissue might slow down the absorption of medication. One aim of this study was to determine if the membrane decreased effectiveness. The researchers implanted the microchip just below the waistline of seven women aged 65 to 70. The procedure can be performed in a doctor’s office with a local anesthetic.

A computer-based programmer established a bidirectional wireless communication link in the Medical Implant Communications Service band to program the dosing schedule with the implant and receive status from the microchip confirming its proper operation.
 
Tracking the women for 12 months, the team showed that the implant delivered the drug teriparatide just as effectively as daily injections, even though the fibrous membrane did form around the device. Treatment improved bone formation and reduced the risk of bone fracture, as evidenced by the presence of biochemical markers signaling bone formation, bone mass, and bone resorption.
 
“And there is much less variation from dose to dose than injections, so it’s safer and more effective in that sense,” Langer said. The device and drug combination were found to be biocompatible with no adverse immune reaction. The chip was removed from participants at the end of the one-year treatment.
 
“A microchip that continues to deliver teriparatide with this or similar consistency and efficiency over 12 to 24 months could improve bone mass, density, architecture, and strength,” said study co-author Robert Neer, founder and director of the Massachusetts General Hospital Bone Density Center.

In an editorial in Science Translational Medicine, author James Watson, founder of the von Liebig Center for Entrepreneurism and Technology Advancement at the University of California, San Diego, wrote that the reliability and durability of the microchip have yet to be established, and it may take a while until the device is clinically used. “But a versatile implantable device that exploits the microchip approach for controlled drug delivery will be well worth the wait for patients for chronic diseases,” he noted.

MicroCHIPS said it is developing new designs of the microchip to include as many as 400 doses per device so it can provide daily dosing for one year or multi-year therapy for less frequent dosing regimens. Components of the original microchip technology, such as the array of micro reservoirs used to contain drug and the first microchip opening mechanism, were developed at MIT and licensed to MicroCHIPS. In addition to osteoporosis, the company is moving ahead with other therapeutic applications in proprietary programs and through strategic partnerships.