Genetic Influences on Efficacy of Methotrexate in a Murine Model of Arthritis
This study aims to determine the effect of a drug transporter on how well the drug methotrexate works in a mouse model of arthritis. Methotrexate is a drug that is used to treat many autoimmune diseases and some cancers. Preliminary data show that genetic variants influence response to methotrexate in kids with juvenile idiopathic arthritis. Methotrexate is removed from the blood by a transporter, so when its function is reduced, there is more methotrexate in the blood. Approximately one in four Americans has a genetic variant that reduces the function of this transporter.
We will give mice without this transporter arthritis, then treat them with methotrexate. We anticipate that the mice lacking the transporter will have a better response to methotrexate than normal mice. We will determine the concentration of the drug in the blood of the mice and use it to find a dose of methotrexate that will provide the same drug level in the mice lacking the transporter as normal mice. This study may help us determine which patients are going to be good responders to methotrexate and could be started with a lower dose to avoid toxic side effects.