Greetings from the TEDMED conference in San Diego, CA. Your blogger is at this conference for the week……….and will post some of the most interesting presentations on this BLOG, next week.
Pain killer: A new class of drugs proves exceedingly effective against the pain of osteoarthritis (seen here in the x-ray of a degenerating knee joint).
Credit: Courtesy of Nevit Dilmen/Wikimedia Commons
A new approach alleviates osteoarthritis pain better than any drug available
MIT Technology Review, October 26, 2010, by Lauren Gravitz — A new class of pain relievers that targets musculoskeletal pain receptors, instead of more general pain pathways, could alleviate osteoarthritis pain better than any drug now on the market, but hurdles remain before it’s approved by the U.S. Food and Drug Administration. Research on the new therapy was published yesterday in the New England Journal of Medicine.
Osteoarthritis occurs when joint cartilage wears down, with the worst cases requiring joint replacement surgery. The pain can be unrelenting, and there’s no real cure. Patients often get through the day by relying on pain relievers, typically starting with over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen. As the pain intensifies and people become inured to the drugs’ effects, they gradually work their way up to opioids such as oxycodone.
The new treatment, called tanezumab, acts on a completely different pathway. While NSAIDs inhibit an enzyme that produces inflammation, and opioids target specific receptors in the central nervous system, tanezumab homes in on musculoskeletal pain receptors. This approach promises fewer side effects, such as internal bleeding, liver damage, and the danger of addiction, which can accompany the alternatives.
Tanezumab, which was developed by Pfizer, is the first in a new class of pain relievers that inhibit sensory neurons, preventing them from transmitting pain signals to the brain. In a clinical trial to assess the intravenous medicine’s efficacy, patients on tanezumab experienced as much as a 62 percent reduction in pain–as much as 40 percent better than the placebo.
“Nothing out there works like this–this is a game-changing molecule,” says Nancy Lane, director of the Center for Healthy Aging at the University of California, Davis, and the study’s lead researcher. NSAIDs and opiates show about half the efficacy of tanezumab (although the current study only compared different tanezumab doses to a placebo rather than to currently available medications). Still, Lane says, “The efficacy was beyond belief.”
Tanezumab works by preventing a protein called nerve growth factor from attaching to sensory neurons, thereby stopping the neurons from transmitting pain signals to the brain. It’s a pathway specifically related to muscle and bone pain, and therefore provides an opportunity for targeted pain relief.
“This really represents a new class of drugs, and it’s been many decades since we’ve introduced a new class of agents for treating osteoarthritis,” says Patrick Mantyh, a professor of pharmacology at the University of Arizona. “It’s an outstanding paper, very thorough, and a beautiful case of coming up with a really novel approach for treating pain and showing a clinically significant result.”
The Centers for Disease Control and Prevention conservatively estimates that about 27 million people in the U.S. suffer from osteoarthritis–a number that represents a huge opportunity for any company that can improve upon existing pain relief. At least four American pharmaceutical companies have therapies in development that inhibit either nerve growth factor or the receptor to which it binds; all are intensely watching Pfizer’s progress.
The study’s results come with a word of caution. Lane and her colleagues completed the trial in 2007. In the years since, Pfizer started a number of phase II and III trials, but has since been ordered by the FDA to suspend them: Ensuing osteoarthritis trials caused a small number of participants to experience so much tissue degeneration that they required joint replacement surgery, and not necessarily on the joint they were undergoing treatment for.
More studies need to be done to determine whether the joint damage occurred because tanezumab was somehow affecting bone or because it was just so effective that the subjects were more active than they should have been and didn’t feel pain to warn them of serious injury. Lane believes it’s the latter. “It works so well that people are going to need to be counseled. Just because they don’t feel pain doesn’t mean their disease is gone,” she says. “Pain is good; it keeps us from doing too much. And this medication is very good, so good that it allows people to do more than they should.”
Getting pain relievers approved by the FDA has always been difficult, since there are so many drugs with a proven safety record and relatively good efficacy already commercially available. In the post-Vioxx era (the drug was approved then taken off the market after it was shown to increase risk of stroke and heart attack), the FDA sets the bar even higher.
Even if it turns out that tanezumab is acting on bone and doesn’t make it through the approval process, Mantyh says, the research is no less important: It proves nerve growth factor has an important role in driving skeletal pain and is thus a good target for pain relief. “In the end, if the drug doesn’t get approved for whatever reason, they have provided clinical data to show that [nerve growth factor] is a major player in driving the pain of osteoarthritis.”
Kevin Koch, the chief scientific officer and president of Boulder, Colorado-based Array Biopharma, says Pfizer should be congratulated on moving this aggressively. “Being the first is always the hardest,” he says. Array is working on its own type of nerve-growth-factor inhibitor, an orally administered version that lasts only 12 hours, rather than eight weeks. So he’s particularly interested in the outcome of tanezumab trials and the FDA’s approval process. “This is a very exciting mechanism,” Koch says. “This is by far the most effective new pain therapy I’ve seen.”
Pain relief: Scientists at MicroTransponder are developing a novel neuro stimulator to treat chronic pain. Small electrodes (blue circles) are injected near the spinal cord, and a PDA controls an external coil on the surface of the skin, powering the electrodes. Credit: MicroTransponder
RFID technology allows neural stimulators to get really small.
MIT Technology Review, by Emily Singer — A tiny injectable implant, smaller than a grain of rice, might one day take the place of large neural stimulators used to treat chronic pain and other neurological disorders. The novel device, under development by MicroTransponder, a Dallas-based startup, owes its small size to the use of RFID (radio-frequency identification) technology like that used to tag clothes to prevent shoplifting.
The device works similarly to spinal-cord stimulators for managing chronic pain. The idea is that the electrical jolts delivered by the device override the neural pain signals being transmitted to the spinal cord. However, the precise mechanism is not yet clear.
Existing devices have a battery and controller implanted beneath the skin, which delivers electrical pulses to a connected set of leads placed near the spinal cord. The MicroTransponder device, in contrast, is wireless and has no batteries. The implanted portion consists of small electrodes and a small coil, which is powered by an external battery-powered coil worn like a cuff on the arm or leg. The stimulation parameters are programmed via laptop or PDA and would be tailored to the individual patient.
Like some cochlear implants and other medical devices, the implant is powered with radio-frequency transmission. Radio waves transmitted by the external coil generate a magnetic field in the internal coil, which powers the electrodes. Adopting technologies from the rapidly advancing RFID world has allowed the researchers to further shrink the device. “Instead of trying to transfer energy from two coupled antennas to do telemetry, which is a common approach for medical devices, RFID is geared to have very small transponders, so you don’t need a large coil,” says Joseph Pancrazio, a program director at the National Institute for Neurological Disorders and Stroke, a government funding agency, in Bethesda, MD, that has given the company small business loans.
The research is still in an early stage. Researchers have developed a prototype device, which they are testing in rats. The device can effectively stimulate peripheral nerves in rats, although it’s not yet clear whether the electrical stimulation alleviates chronic pain. (Scientists assess chronic pain in rats by recording how much the animals eat; a rat in pain won’t eat as much.)
Some scientists are skeptical that the device will be powerful enough to deliver a therapeutic level of stimulation. “The main limitation of any electronic device small enough to be injected into the body is that it must receive enough power to operate its circuitry and provide the required stimulation parameters,” says Gerald Loeb, director of the Medical Device Development Facility at the University of Southern California, in Los Angeles. Loeb has also developed an injectable radio-powered microstimulator, which he says has encountered substantial limitations in range and power.
“We believe we can do it with less power,” says Scott Armstrong, MicroTransponder’s chief technical officer. However, he declined to give further details of the technology for proprietary reasons.
If it does prove successful, the device could have a number of applications. Researchers at MicroTransponder plan to test it as a treatment for tinnitus, a perceived ringing in the ears that is particularly common among veterans with head injuries.