How Tecfidera Works to Reduce MS Relapses Finally Discovered, May Lead to Better Treatments

How Tecfidera Works to Reduce MS Relapses Finally Discovered, May Lead to Better Treatments

How the multiple sclerosis (MS) therapy Tecfidera (dimethyl fumarate) works on a molecular level has finally been uncovered, using a new method that can map a drug’s protein targets. The insights gained may open up new avenues for the development of more specific drugs, based on the same mechanisms, but with fewer side effects.

The study, “Chemical proteomic map of dimethyl fumarate–sensitive cysteines in primary human T cells,” was published in the journal Science Signaling.

“This new technology has given us insights into the therapeutic modulation of the immune system that we could not have obtained with standard approaches,” John R. Teijaro, an assistant professor at The Scripps Research Institute (TSRI) and co-senior author of the study, said in a news release.

Although Tecfidera is the most widely prescribed MS drug available as a pill, researchers have not really understood exactly how it works. This is often the case for drugs that have been around for a while, and dimethyl fumarate is also the main component of the psoriasis drug Fumaderm, which has been used successfully since the 90s. (Tecfidera was approved for relapsing MS by the U.S. Food and Drug Administration in 2013).

Many earlier studies attempted to determine how Tecfidera slows relapse rates in MS, and scientists have suggested that a protein called Nrf2 is the treatment’s main target. The idea is that Tecfidera activates Nrf2, which, in turn, unleashes a forceful antioxidant response. But more recent investigations pointed to it mostly working to reduce the activation of the immune system.

The mapping method that made the new insights possible was developed in 2014 by Benjamin F. Cravatt, chair of the Department of Chemical Physiology at Scripps and the study’s co-senior author. It allows researchers to detect how a drug interacts with proteins by mapping a particular kind of strong link — that between a drug and an amino acid called cysteine, found in almost all proteins.

This amino acid is often involved in drug-protein interactions, and the map produced helped researchers understand which proteins are affected, even in complex biological systems where many thousands of proteins are present.

The Scripps research team discovered that Tecfidera interacts with about 50 different proteins, including enzymes and proteins controlling gene activity. Particularly, the team noticed that many of the proteins were involved in activating immune T-cells, which are known contributors to MS.

Recent studies have suggested that Tecfidera reduces immune activity independent of its actions on Nrf2, an idea supported by the fact that there are cases of patients on Tecfidera treatment who have developed progressive multifocal leukoencephalopathy (PML) — an infection that only occurs in people with weakened immune systems.

Further molecular studies confirmed that Tecfidera prevents the activation of T-cells, and it does so by binding to several proteins on the surface of these cells.

The research team is now using the protein interaction map in attempts to develop drugs that interact only with the proteins found to be most important. Such an approach might lessen side effects linked to Tecfidera treatment.

“We’re interested ultimately in making more selective, site-specific drugs, both to reduce immune activity and to boost it,” Teijaro concluded.

Patrícia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.
Patrícia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.
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  1. Karen andresen says:

    Tecfidera has made my teenager so sick. She had severe abdominal pain and wanted me to end her misery. I’ve heard this from other people. We tried every approach and wanted it to work.

    • Debbie Lai says:

      I had my daughter take Ultimate Flora 50 Billion by RenewLife Probiotics and Acidophlous (refrigerated style) from the outset. Thankfully she didn’t have the side effects. Not sure if the Probiotics helped prevent the side effects, but it’s worth a try possibly. DD, also took peanut butter with each dose since starting it in 2014. Hope these tips help!

    • Mags says:

      I hope she’s doing better now, a bit late now for me to be commenting but for newbies to Tecfidera I would suggest 1 aspirin half an hour before dose, have a reasonably substantial meal and take the Tecfidera in the middle of eating so it’s sandwiched among food. I don’t feel like eating in the mornings but I force myself to have breakfast, skip lunch then have dinner around 8pm so I’m staggering the doses by 12 hours. For me the gastric pain lessened over time but the flushing got worse.

  2. Darlene Young says:

    I have been on Tecfidera since August of 2015.
    I had 2 or 3 flushing episodes in the very beginning, but basically no obvious side effects since then.

    I am stable and thankful that this medication appears to be working for me.

    • Darcy says:

      I know this is a bit late and you probably won’t see it but hopefully this will help others with flushing issues but taking aspirin with every tecfidera dose will completely eliminate flushing. If you are just starting tecfidera it may not completely eliminate it but it will keep it to a tolerable level.

    • I find if you take 325 mg of aspirin and wait 1 hour then take tecfidera the flushing lasts only 10 minutes max . Good luck hope this works for you .
      God bless you 🌹🌹🌹🌹

    • AO says:

      Take med with cheese or yogurt. I was having flashes my fave would be red n it flet as if it was sunburned as well as my scalp. But I listen to one of the RN educator n started eating cheese, yogurt, avocado fatty substance food n Im doing better. Its been weeks n my stomach is still getting use to it. However the abdominal pain has gotten better.

  3. Tina Curtiss says:

    I was taken off Tysabri 3 months ago due to being on it for 9 yrs and now JC positive. My MS symptoms increased significantly but 9 days ago I started Tecfidera and have stabilized again. I had some flushing the first 5 days but no longer. Each of us are different, so is our reactions to the current MS therapies. The key is to find the one that works best for you. You and your neurologist should be able to make an educated guess based on your medical history. Good luck to all in finding the best treatment.

    • Tim Bossie says:

      That is absolutely right Tina. We are all different and react to different drugs in ways that others may not. Unfortunately, it takes a lot of patience, trials and bad experiences some times to find a combination of treatment that help.

  4. jennifer burdett says:

    Thank you all for your comments.
    I’ve been on Tecfidera for 3 months at full dose. My latest MRIs show new lesions on my brain & one on cervical spine.
    Does anyone know how many months the drug needs to be in you, before it’s affective.
    One neurologist thinks it’s not working, the other isn’t worried. I can’t find an answer online.

    • Jane says:

      You have a mind of your own and own your own mind! If you are getting worse stop this poison from entering your body!

    • Alan Macfarlane says:

      Hi my Daughter Stephanie has been on Tecfidera for some years. Now appears it hasn’t worked at all. New lesions opposite side of brain and now down the spine. She starts new treatment Mar 18.
      Regards to all Alan

    • Pearl Nichols says:

      If you have new lesions that medication is not working ypu must change meds. The purpose of these meds are to slow down the progression od the diease meaning no new lesions

    • John Pedroza says:

      Hello Jen,
      My neurologist, a specialist in MS told me it takes 6 months to see the full effect of a particular medication. I was on Avonnex with another neurologist. After a year on avonnex my lesions increased in size.

      Bless you and I wish you well.

      Have A Great Night!
      John Pedroza

    • Cassidg says:

      My neuro wanted to take me off it after 4 months. That was about a year ago. No new lesions. Very few flushing episodes. Im jc virus positive. Heavily monitoring my blood work as i have low lymphocytes and iron levels.

  5. Debbie says:

    Hi Jennifer, I just saw your post and do not know if there is a one size fits all answer. You might want to call the company and ask them. I would guess the company has the best overall data on everything to do with Tecfidera. Each person being different I don’t think there is 1 correct answer is what I am trying to say.

  6. Cheegum says:

    Started Tecfidera a week ago and still on the baby 120 mg dose. I have experienced some upset stomach but nothing as bad as the havoc wreaked by Satan’s Tic Tacs i.e. Prednisone.

  7. Ebon says:

    I have been on Tecfidera for almost 1 year. I have found the best way to take it so you don’t get side effects is to have breakfast as normal (i.e. I have a smoothie) … then at 10am every day i take my first dose with a protein bar (Pure Fit is by far the best one that has worked for me. It needs to have at least 10mg of protein). I have my second one with dinner. No side effects.

  8. Allan W. says:

    I am on day 2 of full strength dose of Techfidera. Had flushing the 1st day of starter dose but less on 2nd day and none since. I always take the pills with a meal (breakfast and dinner). My double vision has stopped completely for now. Hope this helps.

    • Pearl Nichols says:

      Hi Ken
      Exacerbation is also known as a flair meaning new symptoms more numbness tingling etc that have stopped for sometime but even with treatment they come back and they come back usually stronger or some of the symptoms you had when first diagnosised. New lesions cause flair ups

  9. Armando Jimenez says:

    Techfidera has been a blessing for my son who’s been on it for 3 years now. Has not had a relapse since. He finds that flushing isn’t a problem so long as he doesn’t take it on empty stomach.

  10. Belinda Smith says:

    I have been using Tecfidera for 4 years and have had great results according to my MRI’s. I’ve had no new lesions, or active lesions according to my last MRI.I do have flushing a few times a month.I take dosages with food and keeps the abdominal pain away.I am happier with taking a pill
    Than injections.

    I will say it was extremely tough getting through the first 2 months. I had several
    Occasions of vomiting and abdominal cramps. It was worth it.

  11. Danielle says:

    Tecfidera has kept my MS in remission for 5 years. It took a few months to adjust/acclimate to it but eating a bowl of old fashioned oatmeal with milk made it so my stomach always was ok and I rarely flushed. I did shed some extra hair at first but it all came back and it was no big deal. I have been way better on this drug. Even my pain and other symptoms are better! It’s awesome.

    • Darlene Herrera says:

      Thank you for your post Danielle. I started Tecfidera on September 13, 2018, I take a baby aspirin 30 minutes before my dose and get no flushing and I also take with food. I have also been losing some hair since taking this RX, I’m glad to hear the hair loss subsided. I was getting worried. I am also taking CBD oil twice a day to help with my numbness of fingertips. All in all I feel like I’m managing ok so far.


  12. Samantha says:

    I have to say Tec has given me new hope. I’ve been taking it for roughly 18 months. Prior to that my MS was very aggressive, resulting in a relapse every 6-8 months. I couldn’t walk, practically confined to a wheelchair. But now I haven’t had a relapse in 18 months and am able to walk without my walker. Thank God for this. I found I only had minor side effects for the first 6 months (little flushing). But I’m side effect and relapse free for now, and hopefully forever. TG for it!

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