Uncovering the Mystery of Methotrexate

Rheumatologist diagnoses patient with advanced RAHealth care providers are already aware of the ways that methotrexate can help people who have been diagnosed with rheumatoid arthritis. This drug has proven effective at limiting the amount of joint pain that this inflammatory disease causes while also allowing for better joint function. Plus, it is relatively inexpensive as far as treatments go, and it can be taken orally once a week. However, patients must take great care while taking methotrexate.

Methotrexate actually has a long history of usage, since it has been prescribed to patients for more than 60 years. Yet in all this time, health care officials are still unsure exactly how this drug is able to help control the immune system’s attack on the joints of people with rheumatoid arthritis (RA).

Solving the Mystery of Methotrexate

This is where Dr. Nancy J. Olsen, a professor of medicine and head of rheumatology at the Penn State Milton S. Hershey Medical Center in Hershey, Pa., has been working to finally uncover the mystery of methotrexate. With the financial support of the Rheumatology Research Foundation, Dr. Olsen and her team have been studying blood samples that were taken from RA patients who have been prescribed methotrexate. Their goal is to fully understand how this drug actually interacts with a patient’s immune system cells.

For this RA medical research, Dr. Olsen has been collaborating with Dr. Thomas Aune, a well-renowned professor who resides at the Vanderbilt University Medical Center in Nashville, Tenn., her unofficial partner in crime on this project. Dr. Aune has been spending most of her time in the laboratory, trying to identify various patterns in the blood samples. Their discussions have led to a number of new theories about methotrexate and its method of action.

Dr. Olsen: “If we can figure out how methotrexate works, maybe we can figure out how to improve treatments…..”

Methotrexate Method of Action in RA Patients

For this RA clinical study, Olsen’s colleagues had to recruit people with RA symptoms who were currently on methotrexate, or they were ready to start treatment. The team wanted to use blood samples in order to determine how the drug equalized the levels of certain genes and proteins within the immune system cells.

When the red blood cells from RA patients divide and grow, they actually present with the signs of stress and aging. The results of this research suggest that methotrexate not only suppresses the immune system response, but it also alters the profile of an immune cell, rendering the cell normal once again.

Dr. Olsen and her colleagues are also keeping an eye out for activation of the immune pathways in the blood samples taken from their participants. This information would be vital when it comes to reconstructing the most likely pathways of action taken by methotrexate.

Now, these blood tests could show some alterations before the patient actually sees any improvement in their rheumatoid arthritis symptoms. However, this could be beneficial for doctors as they try to predict the outcome of treatment and determine how the patient will react to their medication.

Funding from the Rheumatology Research Foundation

Dr. Olsen is all too thankful that the foundation was willing to give her the grant, as she believes this provided the catalyst her team needed to progress forward in their research. They are now formulating a whole new set of methotrexate-related research proposals.

“We had an idea at an early stage, but we needed support to make those ideas into actual experimental data,” claims Dr. Olsen. “In research, novel ideas are most important, but at the same time, it’s difficult to get new ideas tested. This was the starting money for this new line of thinking.”

While her research team has been focused on the effects of methotrexate, Dr. Olsen does claim that this research should provide further insight into this autoimmune disease and potential new treatments.


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