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.

10 comments

  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!

  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.

  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:

    Hi,
    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.
    Thanks,
    Jen

  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.

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