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In June of 2022, the first systemic treatment for alopecia areata was approved by the FDA. Instead of targeting a local area - on the scalp or elsewhere - and working to confine an inflammatory response from spreading, the drug focuses on the entire body and works to rewire the immune response itself.
Called Olumiant (baricitinib) or Lilly, the oral tablets are only available to adult patients with extreme alopecia and work by a medium of JAK inhibitors, used widespread as treatments to many other autoimmune diseases.
To understand what JAK inhibitors are and how they function in suppressing autoimmune tendencies, one first needs to know what cytokines are and how they play a role in this process.
Cytokines are small proteins that function in cell signaling. After being secreted by cells of the immune response, cytokines serve as tagging molecules to pathogens, calling other cells to the site of infection to digest/destroy the intruder.
There are multiple classifications of cytokines, including chemokines, interferons, interleukins, and more. Interleukins are generally associated with helper T cells, and interferons are associated with antiviral responses.
Because some cytokines cause a greater immune response, there is much research currently being looked into as to whether certain cytokines related to alopecia could serve as treatment therapies. For example, interleukin-17, a cytokine which normally boosts the immune system response, is associated with TH17 cells, so JAK therapy to limit these cells could potentially inhibit interleukin-17 from calling an unwanted response to the site of infection.
So how are JAK proteins related to cytokines?
JAK proteins work to phosphorylate activated cytokine receptors from the intracellular side. This means that a phosphate group is added via a covalent bond to a molecule. Once the cytokine receptor is phosphorylated, proteins known as STAT proteins attach to the receptor and are also phosphorylated. From this step, the proteins travel to the nucleus of the cell, where the reading of genes can be initiated to cause a pro-inflammatory response.
In understanding this process, researchers have come up with a treatment - JAK inhibitors - to stop this process from occurring, thus tamping down an unwarranted immune response.
The inhibitors work by binding to a portion of the JAK protein, preventing the activation and subsequent binding of the JAK protein to the cytokine receptor and therefore preventing phosphorylation of the receptor subunits. Since the receptor subunits do not have the phosphate group attached, STAT proteins are unable to bind and be phosphorylated themselves, ultimately inhibiting the reading of genes involved in an immune response.
In short, a JAK inhibitor works to halt a single process in a multi-step pathway, thereby shutting down the rest of the pathway that normally promotes an immune response.
Because alopecia is the result of an overactive immune response, JAK inhibitors, as proven by the successful and approved new drug Olumiant, serve as important molecules in modulating the immune system and potentially treating the disease.
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Commissioner, O. of the. (2022, June 13).
FDA approves first systemic treatment for alopecia areata. U.S. Food and Drug Administration. https://www.fda.gov/news-events/press-announcements/fda-approves-first-systemic-treatment-alopecia-areata
Lin, C. M., Cooles, F. A., & Isaacs, J. D. (2020, June 11).
Basic mechanisms of JAK inhibition. Mediterranean journal of rheumatology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361186/
Oluminant. (2022).
What is Olumiant® for ALOPECIA AREATA: Olumiant® (baricitinib). What is Olumiant® for Alopecia Areata | Olumiant® (baricitinib). https://www.olumiant.com/alopecia-areata/what-is-olumiant
YouTube. (2017, June 6).
Mechanism of action of JAK inhibitors. YouTube. https://www.youtube.com/watch?v=dnnsqiDjAgM
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