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Investigational medicine

Drug restores hair in patients with alopecia areata

New research ties JAK inhibitor to blocking destruction of hair follicles. 

Alopecia areata,hair loss in a woman

Source: Dr P Marazzi / Science Photo Library

In the open-label clinical trial of 12 patients with more than 30% alopecia-related hair loss, six have so far responded favourably to treatment

Scientists have shown how hair growth is restored when T cells responsible for hair loss in alopecia areata are eradicated using ruxolitinib — a drug approved by the US Food and Drug Administration (FDA) to treat myelofibrosis.

The researchers from the Columbia University Medical Center (CUMC) in New York identified the T cells that surround, damage and eventually destroy hair follicles leading to the hair loss associated with the condition.

The research, published in Nature Medicine (online, 17 August 2014)[1], was sparked by a study four years earlier. That study, which involved 1,000 people with alopecia areata, suggested that “a danger signal” existed in the hair follicles of the participants. The signal draws immune cells to the follicle, which is subsequently attacked. 

“We used that ‘danger signal’, the NKG2D pathway, as our starting point,” says Raphael Clynes, a medical oncologist, who co-led the study while he was an associate professor in the departments of pathology, cell biology, medicine and dermatology at Columbia University Medical Center (CUMC) in New York. “From that point on, our goal was to isolate the specific T cells that contained that receptor, and then show how those cells were singularly responsible for the disease.”

Over the next two years, Clynes and his researchers identified those pathogenic cells, as well as the proinflammatory cytokines they produced. To determine how to block cytokine activity, the team identified some key immune pathways that might be successfully targeted by a new class of drugs called JAK inhibitors. JAK inhibitors, by inhibiting kinase activity, would, in turn, block cytokine-produced inflammation.

The next step involved administering JAK inhibitors to mice with severe alopecia-related hair loss. Clynes’ team worked with two JAK inhibitors, ruxolitinib and tofacitinib – FDA-approved drugs designated to treat myelofibrosis and rheumatoid arthritis, respectively. Within 12 weeks, both drugs completely restored the animals’ hair, with new growth lasting for several months, post-treatment.

For tests on humans, the researchers opted to use ruxolitinib because their work suggested it was less toxic and worked as well as tofacitinib in blocking the relevant pathways. The open-label clinical trial involved 12 participants who had more than 30% alopecia-related hair loss and who used the drug for six months.

“We knew within the first few months that we had hit on something important,” says Clynes, who is now employed by Bristol-Myers Squibb, which was not involved in the research. Six patients out of nine have responded favourably to the treatment, and the final three have just started receiving medication.

A follow-up study is planned to confirm that ruxolitinib is an effective treatment for alopecia. Clynes is now in discussions to secure funding to proceed with either a clinical trial tied to oral-medication, which would involve several hundred participants, or a topical-medication study, which requires establishing a proof of concept and would enlist between 40 and 50 people. 

Clynes sees ruxolitinib as a promising solution to a condition with few options. “The standard of care for alopecia areata has been intralesional steroids, although their efficacy has not been proven rigorously through randomised clinical trials,” he says, noting they do work for many patients but only temporarily. Intralesional steroids also have disadvantages. Each lesion requires multiple injections. “If you have a specific area on the head with significant hair loss, you need a lot of needles, which is hard on patients,” he says, adding that topical steroids do not work well. “But we’re on the way to changing that.”

Citation: The Pharmaceutical Journal DOI: 10.1211/PJ.2014.20066248

Readers' comments (1)

  • JAK Inhibitors is an interesting New Development, I agree, BUT what about:
    Emerging role of Cardiac glycosides for treating alopecia Areata and other types of Hairloss.

    ABSTRACT:

    • Novel discovery that “Cardiac Glycosides” are being potent agents for treating Hairloss
    • The most widely accepted hypothesis is that Alopecia Areata is a T-cell mediated autoimmune condition.
    • The Cardiac glycosides / Bufadienolides : inhibited T-cell activity at a concentration of 0.75 pmol/10(5) cells. This effect is 16,384 x stronger than that of cortisol and 256 x stronger than that of cyclosporin A or tacrolimus. Terness P, Navolan D, Dufter C, Kopp B, Opelz G
    The T-cell suppressive effect of bufadienolides: structural requirements for their immunoregulatory activity. [In Vitro, Journal Article, Research Support, Non-U.S. Gov't]
    Int Immunopharmacol 2001 Jan; 1(1):119-34
    Inventor Alopecia Researher Patents granted UK, FRANCE GERMANY, CHINA, USA and more.

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