JAK inhibitor - Alopecia Areata
JAK inhibitor - Alopecia Areata

ALOPECIA AND JANUS KINASE ENZYMES

Researchers have identified the specific immune cells and primary inflammatory signalling pathways responsible for infiltrating the hair follicle in alopecia areata, forcing them into a dormant state.

Experiments with mouse and human hair follicles showed that oral and topical drugs inhibit the Janus kinase (JAK) family of enzymes.

The JAK family is a suppressor of signalling molecules and plays a role in the immune regulation and growth cycle of the hair follicle.  When the JAK family of enzymes are inhibited, inflammatory signalling is blocked, and the hair follicle regenerates so hair grows back as normal.

JANUS KINASE INHIBITORS AND THE IMMUNE SYSTEM

JAK enzymes can induce inappropriate activation of immune cells that play a critical role in alopecia areata.  JAK enzymes initiate the creation of cells that attack the hair follicle causing inflammation and degradation of the hair shaft.

JAK inhibitors are molecules that lower JAK enzyme activity. In the 1990’s, JAK inhibitors were first studied to help prevent rejection of kidneys after transplant surgery. They were shown to control signalling of interleukin-2, a key pathway that is over stimulated in the rejection of a transplanted kidney.

JAK INHIBITORS AND T CELLS

Alopecia areata is a T cell mediated autoimmune disease.  The T cells that are specifically implicated in alopecia areata are T helper cells.  A higher ratio of T helper cells to T regulatory cells in any area will induce an inflammatory response that can be seen in auto immune diseases such as arthritis and asthma.  When the hair follicles are affected, there will be lesions of hairless areas on the scalp where there has been an infiltration of lymphocytes.

Where there is an imbalance of T cell population, cutting the communication cord with the T cells and the hair follicle would prevent hair loss.  The inhibition of JAK enzymes would prevent the recruitment of T cells to the hair follicle thus cutting the cycle that results in hair loss.

TYROSINE VS JAK INHIBITORS FOR THE TREATMENT OF ALOPECIA AREATA

Tyrosine is able to specifically increase immune signalling molecules that prevent destruction of the hair follicle by moderating T cell activity.  Current JAK inhibitors inhibit both IL-10 and IL -2, which brings about recurrence of hair loss within the treatment period.  Furthermore, discontinuation of treatment results in the return of hair loss.

THE FINAL WORD

Tyrosine can be as effective as a selective JAK inhibitor.  Tyrosine can target IL-2 alone, thus, it can be considered a selective JAK inhibitor.  Currently, tyrosine is used to treat alopecia successfully, but more research is needed to assess a standardised dosage and treatment timescale. Tyrosine is considered a very safe and versatile oral supplement, but it must be used with caution in persons with a history of epilepsy, hyperthyroidism or migraines.  Research should also identify contributing factors to alopecia areata such as zinc, iron deficiency, and vitamin D deficiency.

REFERENCES

  1. Gilhar A, Keren A, Paus R. JAK inhibitors and alopecia areata. The Lancet. 2019 Jan 26;393(10169):318-9.
  2. Beck GC, Brinkkoetter P, Hanusch C, Schulte J, van Ackern K, van der Woude FJ, Yard BA. Clinical review: immunomodulatory effects of dopamine in general inflammation. Critical Care. 2004 Dec 1;8(6):485.
  3. Bakr MA, Nagib AM, Donia AF. Induction immunosuppressive therapy in kidney transplantation. Exp Clin Transplant. 2014 Mar 1;12(Suppl 1):60-9.

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