Treatments for rheumatoid arthritis historically targeted either the inflammatory symptoms or the biochemical processes leading to inflammation. Anti-inflammatories such as ibuprofen and corticosteroids, while providing immediate relief, simply treat the symptoms of inflammation. They are not long term treatments and do not slow progression of the disease. Disease modifying drugs such as methotrexate (originally designed as a chemotherapy for cancer) target the processes that lead to inflammation. The current “gold standard” treatments for RA are the biological drugs that reduce either tumor necrosis factor (TNF) or one of the other inflammation-causing proteins such as interleukin 6 (IL-6) or interleukin 1 (IL-1). These treatments include Enbrel, Humira, Actemera, and several others (see earlier post for list of biological treatments). A large proportion of patients don’t respond well to or at all to these current treatment options. None of the current line of RA treatments target the root causes of RA…probably because the causes remain mysterious. There is no cure for RA.
A reader of my blog recently brought attention to a new line of research that shows promise at targeting underlying processes of RA. In RA, some unknown trigger (see earlier post re. triggers) sets off an attack of the body’s own tissue. This autoimmune response results in inflammation and the destruction of one’s own tissue. The reason TNF and IL-6 blockers like Enbrel and Actemera work is because they inhibit the destructive proteins (cytokines) released during the process (see earlier post on the biochemical processes of RA). But these treatments don’t stop the destructive autoimmune attack, they simply slow it down.
In healthy people, white blood cells die after they serve their role in attacking foreign invaders. In people with RA, white blood cells called macrophages don’t die. The increased macrophages end up releasing extra cytokines like tumor necrosis factor (TNF) and IL-6 which in turn leads to increased inflammation and destruction of healthy tissue.[i] This process is called the Macrophages Model of RA. [ii] A team of researchers working with this model recently published the results of a study in the journal Arthritis and Rheumatism.[iii] A summary of their work is presented below.
One specific protein, called BIM[iv], is involved in the Macrophage Model and is the target of new research and possible treatments for RA. BIM proteins trigger the death of macrophages after they do their regular job of attacking foreign invaders in the body. BIM is shown to be reduced in the joints of RA patients. This shortage of BIM results in an increased number of macrophage white blood cells resulting in increased inflammatory cytokines and the symptoms of RA. These BIM proteins have also been investigated in the treatment of certain cancers.
After documenting a reduction of BIM in people with RA, the researchers set out to test the hypothesis that treating arthritic mice with BIM would reduce the damage caused by RA. An imitation of the BIM protein was used as a treatment for mice who were induced with RA (sorry for those who love animals…all of this type of research involves mice). A news release by Northwestern University described the research results in the following statement:
“When Harris injected his drug into mice with rheumatoid arthritis, it floated ghostlike into their macrophages and bam!, the misbehaving immune cells self destructed. In his research, Harris showed the molecule could prevent the development of rheumatoid arthritis as well as trigger a remission of existing disease. After the drug was injected in animals with the disease, joint swelling was reduced and bone destruction decreased.”[v]
Because of this result, the imitation BIM treatment has been called “Casper the Ghost”. The researchers also noted that there were no adverse side effects noted from the treatment.
While still in the early stages, these researchers hope to develop better ways to deliver the new treatment. Who knows if this groundbreaking research will ever make it to full-fledged treatments in humans. The process from primary research with mice, to clinical trials with humans, to marketable drugs is long, expensive, and fraught with many hurdles. But the results in mice with imitation BIM have been very promising and the fact that the biochemical processes of RA are being better understood by scientists is good news indeed. In the meantime, I’ll keep injecting the TNF blocker Humira.
photo credit: Creative Commons http://www.flickr.com/photos/magnaram/