Featured Research

from universities, journals, and other organizations

Novel Drugs Selectively Target Pathway Important In Rheumatoid Arthritis

Date:
January 19, 2009
Source:
Wiley-Blackwell
Summary:
Methotrexate, a folate antagonist that blocks folic acid activity, is the most widely used disease-modifying antirheumatic drug for rheumatoid arthritis. It enters the cell via several pathways, one of which involves folate receptor, which is highly specific for cells present in the joints of patients with rheumatoid arthritis.

Methotrexate (MTX), a folate antagonist that blocks folic acid activity, is the most widely used disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis. It enters the cell via several pathways, one of which involves folate receptor β (FRβ), which is highly specific for cells present in the joints of patients with rheumatoid arthritis (RA).

During the last two decades, a second generation of folate antagonists has been designed to address some of the limitations of MTX, which include adverse side effects and resistance. A new study examined the capacity of several of these new drugs to determine whether they could selectively target cells that express FRβ.

Led by Gerrit Jansen of the VU University Medical Center in Amsterdam, researchers analyzed FRβ expression from biopsy samples from the knee joints of RA patients before and after four months of treatment with MTX and from controls. These experiments confirmed that FRβ expression is highly specific to activated macrophages (a type of immune cell that plays a role in the inflammatory response in RA) in the synovial membrane of RA patients.

The researchers went on to examine new folate antagonists to determine which ones would most likely be beneficial in treating synovial inflammation. Several of these agents showed a markedly higher binding affinity for FRβ compared to MTX, which has a high affinity for entering cells via another pathway known as reduced folate carrier (RFC). This pathway is found throughout the body, however, and is therefore not specific for synovial cells.

Researchers also examined whether two of the newer drugs would inhibit growth of FRβ-expressing cells and found that one of them, BCG 945, accomplished this at low concentrations. Interestingly, the uptake of BCG 945 was inhibited by the addition of folic acid. “In this context, it may be anticipated that, for example, fortification of food with folate may reduce the activity of this folate antagonist, whereas restriction in dietary folate intake could further enhance the therapeutic efficacy of these types of drugs,” the authors state. BGC 945 was originally discovered at the Institute of Cancer Research in London, and is now known as ONX 0801. Onyx Pharmaceuticals has an exclusive worldwide license to this compound.

They note that although MTX is the drug of first choice in the treatment of RA, its efficacy can be improved. “Further evaluation of folate antagonists with properties of high binding affinity for FRβ and low affinity for the RFC may pave the road for a more selective targeted therapy of activated synovial macrophages,” they conclude.

In an accompanying editorial in the same issue, Christoph Fiehn of the Center for Rheumatic Diseases in Germany notes that folate antagonists remain the key to RA treatment, both now and in the future. “Antifolate drugs that, unlike MTX, are FRβ-specific would have a stronger effect on synovial macrophages and a weaker effect on other types of cells that take up MTX by the ubiquitously expressed RFC,” he explains. “A higher therapeutic effect and a lower rate of side effects of FRβ-specific antifolates as compared with MTX could possibly be the result.”


Story Source:

The above story is based on materials provided by Wiley-Blackwell. Note: Materials may be edited for content and length.


Journal References:

  1. Fiehn et al. The future of folic acid antagonist therapy in rheumatoid arthritis. Arthritis & Rheumatism, 2009; 60 (1): 1 DOI: 10.1002/art.24216
  2. Joost W. van der Heijden, Ruud Oerlemans, Ben A.C. Dijkmans, Huiling Qi, Conny J. van der Laken, Willem F. Lems, Ann L. Jackman, Maarten C. Kraan, Paul P. Tak, Manohar Ratnam, Gerrit Jansen. Folate Receptor %u03B2 as a Potential Delivery Route for Novel Folate Antagonists to Macrophages in the Synovial Tissue of Rheumatoid Arthritis Patients. Arthritis & Rheumatism, January 2009; 60:1; pp.12-21

Cite This Page:

Wiley-Blackwell. "Novel Drugs Selectively Target Pathway Important In Rheumatoid Arthritis." ScienceDaily. ScienceDaily, 19 January 2009. <www.sciencedaily.com/releases/2009/01/090113174544.htm>.
Wiley-Blackwell. (2009, January 19). Novel Drugs Selectively Target Pathway Important In Rheumatoid Arthritis. ScienceDaily. Retrieved October 1, 2014 from www.sciencedaily.com/releases/2009/01/090113174544.htm
Wiley-Blackwell. "Novel Drugs Selectively Target Pathway Important In Rheumatoid Arthritis." ScienceDaily. www.sciencedaily.com/releases/2009/01/090113174544.htm (accessed October 1, 2014).

Share This



More Health & Medicine News

Wednesday, October 1, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Pregnancy Spacing Could Have Big Impact On Autism Risks

Pregnancy Spacing Could Have Big Impact On Autism Risks

Newsy (Oct. 1, 2014) A new study says children born less than one year and more than five years after a sibling can have an increased risk for autism. Video provided by Newsy
Powered by NewsLook.com
Robotic Hair Restoration

Robotic Hair Restoration

Ivanhoe (Oct. 1, 2014) A new robotic procedure is changing the way we transplant hair. The ARTAS robot leaves no linear scarring and provides more natural results. Video provided by Ivanhoe
Powered by NewsLook.com
Insertable Cardiac Monitor

Insertable Cardiac Monitor

Ivanhoe (Oct. 1, 2014) A heart monitor the size of a paperclip that can save your life. The “Reveal Linq” allows a doctor to monitor patients with A-Fib on a continuous basis for up to 3 years! Video provided by Ivanhoe
Powered by NewsLook.com
Attacking Superbugs

Attacking Superbugs

Ivanhoe (Oct. 1, 2014) Two weapons hospitals can use to attack superbugs. Scientists in Ireland created a new gel resistant to superbugs, and a robot that can disinfect a room in minutes. Video provided by Ivanhoe
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins