The future may hold new treatment options for alopecia areata

Alopecia areata hair loss information for men and women
Alopecia Areata 
Alopecia Areata Biology
Alopecia Areata Treatments

  Future Treatments for Alopecia Areata
 

Alopecia areata is a non-scarring, inflammatory hair loss disease. Currently, the majority view is that it is a T-cell mediated auto immune disease. However, even after considerable research, which has certainly increased our knowledge of the etiology and pathogenesis of the disease, many issues remain unresolved.

Most researchers are now of the view that alopecia areata could have multi-factorial causes, contributing to its susceptibility, onset, progression and maintenance. This has an important bearing on the focus of today’s research – the identification of the gene or genes, directly linked to all aspects of the disease. Also, one, among many factors, may be a predominant cause. Some individuals may be genetically predisposed to alopecia areata and for others it could primarily be toxins in the environment.

If it is accepted that alopecia areata is an inflammation mediated disorder then several new approaches to treatment open up for experimentation.

Current therapies are mainly immunosuppressive or immunomodulatpry. Immunosuppression attempts to prevent entry of the inflammatory cells into the skin and the follicle using steroids orally, interlesionally and through injections. Immunomodulation, by drugs such as contact sensitizers or PUVA therapy, change the skin environment in order to lessen the action of the inflammatory cells. However, these therapies aim at suppressing the inflammation and are not successful in combating the underlying causes.

Immunomodulatory drugs have been used successfully on mice and rats to achieve remission. Since there is evidence of a good correlation between rodent models and human alopecia areata, such treatments should be theoretically successful on humans.

Minoxidil and partly cyclosporine and tacrolimus, directly promote hair growth. Such direct action agents are sometimes used as secondary therapy. However, due to side effects, non-specific action and some treatment failures, attempt is on to develop better therapies and drugs. It is hoped that with better understanding of immunosuppression, immunomodulation and the drugs used in them, more refined and potent drugs will be available in the future for treating alopecia areata.

In order to devise an effective therapy there has to be a proper understanding of the cycle of the pathogenesis and the maintenance of the disease, for which rodent models have been found to be very useful. In rodents the onset of alopecia may be a series of events but the disease continuation could be a cyclical process. This is particularly important since the morphological target, the hair follicle, has a cycle of proliferation and regression. Additionally, an understanding of the molecular mechanism that regulates follicle development is essential for developing new therapies.

To devise an effective therapy, it is essential to identify the stages in the cycle where therapeutic intervention would be most effective. In the hair follicle cycle there are four key events. They are:

  1. The exogenous, endogenous, normal or abnormal expression of the hair follicle antigen on presentation to the immune system.
  2. Antigen presentation, costimulation and activation of responsive lymphocytes by antigen presenting cells or APCs.
  3. The migration to and infiltration of hair follicles by the activated inflammatory cells.
  4. The effect of the inflammatory cells on the hair follicles.

    Each of these events is vulnerable to therapeutic intervention. Also, secondary to the hair follicle cycle, is the possibility of tolerizing, deleting or modulating the reactive lymphocyte clones.

Future Treatments

Some of the latest approaches in alopecia areata therapy are now discussed below.

1. In theory, it is possible to modulate autoimmune inflammation in several ways. An improved understanding of the inflammatory mechanism and the drug action upon them may enable development of more specific therapies. Studies on contact sensitizers have shown that better response could be obtained by changing the skin bio-chemical environment. Interleukin injections or the administration of their cDNA sequences could inhibit the entry of inflammatory cells into the skin and hair follicles. Or else, treatments could be developed which promote hair growth despite the inflammation.

2. The biggest challenges in treatment remain the identification of lymphocyte clones reactive for hair follicle antigen epitope and the blocking of their production or increasing the tolerance. In auto immune diseases oral tolerance is suggested, but without identifying the antigen such an approach is not possible.

3. Another treatment mode could be blockade or modulation of antigen presentation and costimulation by antigen presenting cells to the responsive lymphocyte clones in alopecia areata.

4. Studies have shown that it might be possible to prevent migration of inflammatory cells from activation sites to the follicle and skin, even after activation of the lymphocytes. Initial investigations where CD44v10 were targeted with MoAbs indicate that such prevention could be an effective cure for alopecia areata. Additional targets could be other activated cell surface markers and variants expressed during migration. Such treatment modes may be used as a cure as well as a preventive measure in the case of individuals predisposed to alopecia areata.

5. Techniques are also being devised to deal with the disease, once the hair follicle inflammation has set in. One of the potentially complicated therapeutic techniques could involve inhibiting or modulating the expression of the targeted antigens in the anagen phase hair follicles. Alternatively, the treatment could involve the masking of the expression of these threatened antigens. Besides modification of the harmful antigen expression, caused by inflammation, prevention of expressions of MHC antigens in the hair follicles may prevent alopecia areata injury to continue indefinitely.

6. Ultimately, the aim may be to target the mechanism by which the inflammatory cells adversely affect hair follicle growth. This includes Fas-Fas ligand interaction, prevention of granzyme and perforin action, oxygen radical neutralization and alteration of the cytokine receptor and cytokine environment.

Conclusion

In short term, more refined and potent drugs will aim at modulating hair follicle inflammation and promoting hair growth. In the midterm, cytokines, antigens, antibodies and other factors will be targeted at aspects of the disease. In long term, however, the target would be the offending genes directly linked to disease susceptibility and the disease cycle mechanism and the genes able to modify the severity of the disease.



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