Experimental Therapies May Hold Key To Future Pain Treatment
Regenerative remedies are now being studied to aid in joint repair and rebuilding.
The treatment of arthritis and damaged joints is about to enter the era of regenerative orthopedics, in which physicians use detailed knowledge of your own cells, proteins and DNA to help you fight inflammation, repair the immune system, and rebuild joint cartilage.
Although most of these experimental therapies are still in the research lab or in early stages of clinical testing, they hold the promise of earlier diagnosis, more effective medications, and better results. Following are three new treatments to keep your eye on.
Medicines That Match Your Genes
Finding the best medication to manage rheumatoid arthritis is often a long and frustrating road of trial-and-error lasting a year or more. Doctors don’t know which drug you’re likely to respond to, so they give you one, then another, until the best candidate eventually emerges. But with some of the newer medications—like the biological agents Enbrel, Remicade, and Kineret—this guessing game can get expensive, and expose you to a variety of unwanted side effects.
But this guesswork may soon be unnecessary, if work being done at Interleukin Genetics Inc. bears fruit. Researchers at this Waltham, Mass.-based pharmaceutical company are developing a test that gives doctors a quick genetic profile of specific genes in your immune system, so that they can determine, in advance, which medications will have the best chance of working for you.
“Just as the genes that code for eye color vary from person to person, so do those that code for the proteins in your immune system,” says Kip Martha, M.D., vice president for Clinical Research & Development and chief medical officer at Interleukin. “It is this genetic difference that explains, in part, why the same drug may be effective in one person, but not in another.”
The science of using knowledge about your genes to choose the right medicine is known as pharmacogenetics, and researchers like Dr. Martha are focusing on a half-dozen proteins in the immune system involved in causing inflammation—especially interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-A). If they can help doctors determine, upfront, which variation of these proteins you make, you’re more likely to get the right medication and dosage from the start, and get your arthritis under control sooner.
Replanting The Immune System
Many forms of arthritis are auto-immune diseases, in which the “attack cells” of your immune system have lost their ability to distinguish between friend and foe and end up attacking healthy parts of your own body. Though researchers have not been able to repair these wayward cells, they are having early clinical success at clearing out these bad actors and helping patients grow a new immune system using stem cells harvested from their own body.
“We’ve had success helping patients with lupus, scleroderma, rheumatoid arthritis and other auto-immune diseases rebuild their immune systems,” says Richard Burt, M.D., Chief of the Division of Immunology, Northwestern University Medical Center. “Although it’s too early to know if we’ve provided a permanent solution, we now have patients with normal, functioning immune systems five years after treatment.”
Before beginning the treatment, known as “autologous stem cell transplantation,” doctors first take out whole blood, filter out the stem cells (less than 1 percent of blood cells), and freeze them for later re-use. Then high doses of drugs are given to wipe out the faulty immune system, killing cells in both the blood and bone marrow. Once cleansed, the stem cells, previously banked, are re-infused.
“It takes about eight to 12 days for many parts of a new immune system to get re-established,” says Dr. Burt. “However, some types of cells, such as lymphocytes, take longer, requiring up to a year before being present in large numbers.”
These experimental treatments are not without risk—such as the new immune system not “taking” and infection, bleeding and blood clots—but they do show promise beyond a simple “re-boot” of the immune system.
“In some of our lupus patients, who had significant damage to their hearts, lungs and kidneys, their organs have essentially returned to normal a year or so after treatment,” says Dr. Burt.
Building New Cartilage
Today, new joints are fashioned using metal and plastic, but in the not too distant future, they may be made using your own cells and knee cartilage taken from animals.
Much of the current research on “regenerative” knee repair focuses on finding ways to mend the small holes or tears in cartilage suffered by competitive athletes. One group of researchers at Genzyme, a Massachusetts company, has developed a method of taking small amounts of healthy knee tissue, sent in by surgeons, isolating key cartilage cells, multiplying their number, and then sending back the tissue for use in “spot” repair. These newly amplified cells are injected beneath a thin layer of connective tissue (periosteum) that has been sewn over the defect.
Other researchers, at Harvard Medical School, are trying to repair similar defects using sponge-like scaffolds made of collagen. “These scaffolds provide a kind of 3-D latticework to hold the new cartilage cells in place as the joint is healing as it is being used,” says Julie Glowacki, Ph.D., professor of Orthopaedic Surgery at Harvard.
In addition to repairing athletes, Dr. Glowacki’s work also holds promise for very young patients who may be born without joints. Her group’s strategy is to take an equivalent-sized knee from a pig, cleanse it of all animal cells, and then use the inert joint as a framework that can be repopulated with the infant’s own cartilage stem cells.
This procedure shows future potential, but its applicability to osteoarthritis, most experts agree, needs further research.
Promising But Still Unproven
Though much of this work holds promise, it’s important to remember that it also carries significant and unknown risks. By definition, these are clinical research trials, many in the earliest stages in which basic issues of safety and effectiveness are still being investigated. Larger, more comprehensive studies need to be performed before any of these treatments, now waiting in the wings, ever take center stage.