I mentioned in a post last week that I was reading a book called Living with Itch by doctors Gil Yosipovitch and Shawn G. Kwatra. Well I’ve since finished it and determined it’s another book that I think everyone should read.
While reading said book I came to the following image:
As I stared at my own palms, which do look remarkably like that illustration (as in I would make a palm reader dizzy trying to interpret all my lines), I pondered about this protein, filaggrin, and about all of us filaggrin-lacking individuals. This led me to wonder if there were existing treatments out there to replace filaggrin in those deficient.
But first, I had to understand what filaggrin does. Cue google scholar searching for studies! Filaggrin is a protein that binds keratin fibers together. Keratin is the protein that helps create the structure of the outer layer of our skin (and nails and other things). So not having functioning filaggrin means that outer skin barrier is not as strong and impervious to the external environment (germs, mechanical stressors like scratching, chemicals, temperature, water retention, etc).
Armed with that knowledge I did a cursory search which brought me to two studies, one in 2014, and one brand spanking new one done this year. The 2014 one looked into filaggrin injections, but I’m getting ahead of myself. To start, the study (done presumably in Europe as it talks about Europeans in particular and as I could only access the study’s abstract) gives background information that 1 in 10 European people have this filaggrin (FLG) loss of function mutation (or what they call a LOF mutation) and that so far this LOF mutation is the biggest genetic risk of atopic dermatitis. They also give other fun likelihoods like that someone with said mutation is more likely ” to develop asthma, to have more severe and more persistent disease, to have allergic sensitizations, and to develop eczema herpeticum”. At this point you may be thinking, ‘all of us FLG LOF’ers are off to a rough start!’ The study then went on to describe why they think filaggrin replacement therapy may help with eczema management (specifically atopic dermatitis, but I’m going to continue using the blanket term of eczema from now on). Basically they talk about how gene replacement therapy of this protein is difficult because the protein is so large and they need to get it through the stratum corner layer of the skin into the cytoplasmic space for it to work. So instead of trying to inject the big protein into the skin, they did some science-magic and used some mouse genetic material linked to a compound that could penetrate cells (a peptide) to make a recombinant protein (which can help get a mutant gene to express the normal function, in this case getting filaggrin to bind keratin fibers together). They tested their work on cell cultures, flaky mice tails, and human skin equivalents and results showed that the flaky tails’ stratum corneum (the outermost layer of the skin) seemed to be restored. They ended the study by saying that there would need to be further studies to determine how safe this would be for humans, as well as things like how much to use, how well it works, and how long to use it, etc. They also noted that though mice didn’t have any problems with the foreign protein injected into their tails, that there is still a possibility that humans’ skin/immune system could reject the forgiven material.
The newer study, rather than trying to inject filaggrin into the skin, took the approach of trying to create a nutritional supplemental to ingest (as they were particularly interested in making a convenient and safe treatment, especially for children). They noted that an amino acid called L-histidine gets used in filaggrin production, and when the filaggrin gets broken down, the L-histidine is released and used as a natural-moisturizing factor (or NMF) and is said to “contribute to barrier function through skin hydration and maintenance of stratum corneum acidity” (hey look, skin acidity mentioned once again). This study also goes on to mention how eczema may be caused by either the FLG mutation or messed up profilaggrin processing but either way can lead to the skin barrier issues we see with eczema, and for either issue the L-histidine amino acid has a beneficial effect. Their overall results were that an L-histidine supplement once a day for 4 weeks showed positive changes to eczema and those benefits lasts even when the L-histidine was discontinued. They even said that their results indicated using the L-histidine was on par with using a mid-potency topical steroid while being steroid free (so none of the side effects)!
Both the L-histidine supplement and the filaggrin injection sound extremely promising and exciting for the world of people living with eczema, though I, in particular am leaning towards the supplement, if I had my pick (I would love to be part of the study for L-histidine, but that will have to wait until I’m done breastfeeding).
Irvine AD. Crossing Barriers; Restoring Function? Filaggrin Protein Replacement Takes a Bow. Journal of Investigative Dermatology. 2014 Feb; 134(2): 313-314.
Sandilands A, Sutherland C, Irvine AD, McLean WHI. Filaggrin in the frontline: role in skin barrier function and disease. J Cell Sci. 2009; 122: 1285-1294.
Tan SP, Brown SB, Griffiths CEM, Weller RB, Gibbs NK. Feeding filaggrin: effects of L-histidine supplementation in atopic dermatitis. Clin Cosmet Investig Dermatol. 2017; 10: 403-411.