| > | | | | human rheumatoid arthritis patients and found that it |
| Rheumatoid arthritis (RA) is a chronic inflammatory | | | | reduced the processes associated with inflammation |
| autoimmune disease that affects 2 million Americans. It | | | | and abnormal growth in the joints. |
| is not a benign disease. Up to half of those with the | | | | Gleevec is the brand name of imatinib, a drug |
| disease are disabled after 15 years due to crippling | | | | produced by the pharmaceutical company Novartis |
| deformity. Many of the drugs currently used to treat | | | | AG. It is part of a class of drugs called kinase inhibitors, |
| rheumatoid arthritis (RA) were originally used to treat | | | | which act by blocking communication signals between |
| different kinds of cancers. | | | | cells. These signals, when they go awry, are often at |
| The first example is methotrexate. This drug is an | | | | the root of diseases such as cancer and autoimmune |
| immunosuppressant that inhibits dihydrofolate | | | | conditions. |
| reductase. By doing this it inhibits the growth and | | | | Gleevec targets kinase gene mutations seen in chronic |
| proliferation of lymphocytes which are important cells | | | | myelogenous leukemia or CML (a bone marrow |
| involved in the autoimmune process. | | | | cancer) as well as certain types of stomach cancers. |
| Another example is azathioprine (Imuran). This drug | | | | The same kinases turn out to play a critical role in |
| inhibits T-lymphocytes, a population of lymphiocytes | | | | rheumatoid arthritis. |
| that are important in the initiation of autoimmunity. | | | | William Robinson, senior researcher, said that the field |
| Cyclophosphamide (Cytoxan) alkylates and crosslinks | | | | of autoimmune disease research has been trying to |
| DNA essentially poisoning cells. Neither azathioprine nor | | | | develop kinase inhibitors for more than a decade. "We |
| cyclophosphamide are used much anymore for | | | | were very surprised that Gleevec worked as well as it |
| rheumatoid arthritis because of toxicity issues. All three | | | | did," said Robinson. "It just seemed too simple." The |
| drugs
methotrexate, azathioprine, and | | | | results are especially encouraging since the drug is |
| cyclophosphamide are still used to treat various | | | | already FDA-approved, and has relatively few side |
| cancers. | | | | effects." |
| More recently, biologic treatments have been used to | | | | We have taken a very potent kinase inhibitor and |
| treat RA. One biologic treatment that has performed | | | | discovered that it works very well for an autoimmune |
| well in RA is rituximab (Rituxan). This drug is | | | | disease," said Robinson. "The significance is twofold. |
| considered one of the drugs of choice for the | | | | First, it might provide insights into the mechanisms |
| treatment of non-Hodgkins lymphoma. Rituximab | | | | underlying rheumatoid arthritis by figuring out what |
| depletes a population of B cells called CD20. CD20 | | | | Gleevec inhibits. Second, he added, it might |
| cells are instrumental in the perpetuation of RA. | | | | represent a new therapeutic approach to rheumatoid |
| A recent intriguing study suggests another anti-cancer | | | | arthritis and other autoimmune diseases. The kinases |
| agent, Gleevec, may have promise in RA. Gleevec is | | | | the drug inhibits likely play a role in other autoimmune |
| currently used to treat leukemia and some | | | | diseases, such as scleroderma, psoriasis and |
| gastrointestinal cancers. | | | | inflammatory bowel disease. |
| Researchers at the Stanford University School of | | | | Robinson said he hopes that in the near future, clinical |
| Medicine, led a team that set out to find drugs that | | | | trials will be conducted that look at the drug's |
| might provide additional benefit to rheumatoid arthritis | | | | effectiveness for a range of autoimmune diseases. |
| patients. They screened a range of drugs in mice that | | | | (Paniagua RT, Ho PP, Chan SM, Changf A, Higgins JP, |
| have a condition similar to human rheumatoid arthritis. | | | | Tomooka BH, Thomas FM, Song JJ, Goodman SB, |
| In their study, Gleevec almost completely prevented | | | | Lee DM, Genovese MC, Utz, PJ, Steinman L, Robinson |
| the development of a rheumatoid arthritis-like disease | | | | WH. Selective tyrosine inhibition by imatinib mesylate |
| in mice. The drug also halted the progression of | | | | for the treatment of autoimmune arthritis. J Clin Invest. |
| established disease, significantly reducing the amount | | | | 2006; 116: 2633-2642). |
| of inflammation and bone destruction around the joints. | | | | Note: Part of this story was adapted from a news |
| The researchers also tested Gleevec on the cells of | | | | release issued by Stanford University Medical Center. |