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MIT researchers and colleagues are developing a new technique to treat rheumatoid arthritis that involves bombarding the affected joint with subatomic particles. The technique could be up to 10 times cheaper than surgery, the current alternative, and would require little if any hospitalization.
Recently the researchers, led by Associate Professor Jacquelyn C. Yanch, finished building the machine that will produce the particles-neutrons-used in the therapy. They hope to create their first beam of neutrons this month.
Dubbed Boron Neutron Capture Synovectomy (BNCS), the technique involves two steps. First, a compound containing boron is injected into the arthritic joint. There it concentrates in the synovium, the tissue that becomes inflamed as a result of the disease.
A beam of neutrons is then directed at the area. The neutrons are absorbed by the boron, which splits into two highly energetic particles that destroy the boron-heavy synovial cells while largely sparing
adjacent healthy cells.
Currently the researchers are testing a promising boron compound and fine-tuning the accelerator. "The work is still in its early stages," emphasized Professor Yanch, who holds joint appointments in the Department of Nuclear Engineering and the Whitaker College of Health Sciences and Technology. She is developing BNCS in collaboration with researchers from Harvard Medical School at Brigham and Women's Hospital, and with Newton Scientific, Inc. Several MIT students are also involved.
Rheumatoid arthritis is characterized by inflammation of the synovium, the inner layer of the joint. There is no cure for the disease, which affects some 3.6 million Americans, but the majority of sufferers can find relief from the resulting pain and swelling by treatments including drugs like aspirin.
Sometimes, however, the synovium is unresponsive. Because chronic synovial inflammation can lead to destruction of the joint, such patients require surgical removal of the offending tissue.
But surgery comes with problems of its own. For example, it's difficult to remove all of the synovium from the nooks and crannies of the joint, and prolonged hospitalization and rehabilitation are often required.
Another approach widely used in Europe, Australia and Canada involves injecting a radioactive fluid into the joint. High-energy particles emitted from the fluid then destroy the synovium. But the technique, known as radiation synovectomy, is not widely used in the US because the radioactive fluid almost always leaks into and damages healthy tissues like lymph nodes.
The MIT technique will have the same end result-removal of the synovium-without the disadvantages associated with surgery and radiation synovectomy.
For example, in contrast to surgery, BNCS does not require cutting into the joint, so the researchers believe it could be performed on an outpatient basis and would require no rehabilitation. It could also be much less expensive. "We expect that the cost of a BNCS procedure will be similar to that for radiation synovectomy, which is about $2,500," said Professor Yanch. The average cost for surgery, not including physical therapy, is between $5,000 and $25,000.
This cost differential is even more important because none of these treatments is necessarily permanent. The patient gets two to five years of relief before the synovium regenerates and inflammation begins anew. "Remember, these therapies are only treating the symptoms of arthritis. There is no cure yet," said Dr. Yanch, the W.M. Keck Career Development Associate Professor in Biomedical Engineering.
BNCS is preferable to radiation synovectomy because it does not use radioactive materials that could leak to surrounding tissues.
Could the BNCS neutrons be dangerous to healthy tissue? "They're relatively harmless," Professor Yanch said. "Certainly some neutrons will hit healthy tissue, but you really have to have the boron there to have enough energy release to cause considerable damage."
And experiments conducted by the team have shown very little boron uptake in cartilage (a tissue next to the synovium), but "very, very high levels of uptake in synovial tissues," Professor Yanch said. Those high levels also help prevent damage to healthy tissues "because you don't have to leave the [neutron] beam on as long" to kill the synovial cells, she said.
Continuing work on BNCS involves developing and testing a suitable boron compound and fine-tuning the accelerator.
Professor Yanch said that to date the group has identified "a very nice boron compound" provided by Professor Alan Davison of the Department of Chemistry. "The next step, which we will be starting soon, is to test uptake of this compound in a [living] animal," she said. (Experiments so far have been conducted on excised samples of human synovium and cartilage in a dish. The animal tests will be conducted with rabbits.)
Other members of the team are working on the accelerator, which is about 10 feet long. Some are testing the newly built device, while others are modifying it for BNCS.
Modifications are necessary because the machine was not built specifically for BNCS, but for a related therapy for cancer known as Boron Neutron Capture Therapy (Professor Yanch is principal investigator for the new accelerator and both of its potential applications). And although the two therapies follow the same general procedure, there are some differences.
For example, BNCS requires a "softer" neutron beam than the cancer therapy because the synovium is relatively close to the surface of the skin (as compared to a deep-seated tumor). Another modification will allow doctors to maneuver the neutron beam to different body parts, rather than having a patient hold his or her knee, say, in an awkward position for treatment.
Though clinical trials for BNCS "are still years away," said Professor Yanch, the researchers are optimistic about the technique's potential and progress so far.
MIT graduate students involved in the work are Emanuela Binello and Brandon W. Blackburn (both in nuclear engineering), and William B. Howard and Haijun Song (both in physics). Undergraduates are Jennifer L. Daigle (a senior in nuclear engineering), Michelle N. Ledesma (a junior in nuclear engineering), Amy Ly (a sophomore in nuclear engineering), and Suzanne M. Sears (a senior in physics).
In addition, the two researchers from Newton Scientific, Ruth Shefer and Bob Klinkowstein, are MIT graduates.
The work is funded by the Department of Energy and the Idaho National Engineering Laboratory.