Teontor (Ted) Simakou is the lead researcher on a project at the University of the West of Scotland. He has just completed, and had published, his literature review in which he has been scoping out the Alopecia Areata research landscape.  His paper was a very interesting read so we thought we’d ask him all about it!

Ted, you’ve recently completed a literature review for your project which has been published in the Journal of Autoimmunity.  I’m guessing you have been doing a lot of reading about Alopecia Areata!  It’s probably best to start from the beginning, what is Alopecia Areata?

Alopecia Areata usually manifests as small patches of hair loss on the scalp, and sometimes on the beard or body hair.  The hair loss can spread throughout the scalp (Alopecia Totalis) and in many cases throughout the body (Alopecia Universalis). As with all other non-scarring alopecias, the hair loss in Alopecia Areata originates from damage of the lower part of the hair follicle and impairment of the hair growth cycle.

What is it that damages the lower part of the hair follicles?

For many years scientists studied scalps with Alopecia Areata and observed that there were immune cells (particularly T cells), infiltrated around the lower part of the hair follicles during their active growth stage (anagen).  Many other studies confirmed involvement of the immune system by studying the genetics and inflammation patterns in Alopecia Areata patients. The evidence made scientists link Alopecia Areata with autoimmunity, a process where the defence responses of an organism are targeting its own healthy cells and tissues. 

Hair follicle cells do not like inflammation. In healthy scalps, during the active growth stage, the hair follicles hide away from the immune system by lowering the production of proteins that the immune cells can detect. They also produce a variety of signals that can “switch off” any activated immune cells in the vicinity.  But in Alopecia Areata follicles, due to the influence of multiple genetic variants, multiple environmental factors, and inflammation itself, the hair follicles lose this protection ability and the immune cells begin to infiltrate around them.  When that happens the hair growth cycle is impaired, the active growth stage stops, and the hair falls and doesn’t grow back. The immune responses can then spread to other hair follicles, resulting in widespread hair loss.

Wow, there is so much going on there!  Genetics, environmental, inflammation… no wonder the hair follicle loses its protective ability.  Do we know what the cause of the autoimmunity in Alopecia Areata is?

The autoimmunity towards the hair follicles is linked to the genetics that predispose someone for developing the disease, as well as many environmental factors that act as fuel for that genetic predisposition.  Many gene variants control production of proteins that are essential for immune processes, such as immune cell development and activation, communication and tolerance. Where mistakes occur in immune cell communication, then they can get activated toward “self” cells, and they start targeting them.  There are many gene variants that could also impair hair follicle functioning, such as those involved in the pigmentation of hair, antioxidant production and protection from the immune system.   Some of the environmental factors that contribute to disease development include oxidative stress, infectious agents like bacteria and viruses, diet and microbiome, and anything that would support an inflammatory environment in the body.

Does this understanding help when it comes to treating Alopecia Areata?

Because there are many genes and environmental factors involved, it is very difficult to predict when and how the hair loss will occur. There is variance in disease start and progression in different patients, and even in members of the same family.  The difficulties for predicting the start and development of Alopecia Areata make the prevention and treatment of the condition difficult.  

However, if Alopecia Areata begins, there are available treatments and it is important that the hair loss is treated correctly in early disease stages. Because of its autoimmune nature, treatments should target the immune responses and the inflammation.  Hair loss is a symptom of such processes, so by targeting hair follicles alone with pro-growth agents for example, is not enough and can allow the autoimmunity to establish. Many treatments such as JAK inhibitors, contact sensitizers (like DPCP) and other immune-suppressive drugs work well and provide good treatment for the majority of Alopecia Areata patients.

But the efficacy of treatments is also depended on many factors:

Time: Many treatments work more efficiently and provide good re-growth if applied early in disease.  In early disease stages, targeting the T cells alone may be therapeutic. But with time and in advanced stages many more cells are involved, the immune responses are well-established, there is antibody development and T cell disbalances, all that need to be targeted differently with multiple treatments. Also, like in the androgenetic alopecia (male pattern hair loss), over the course of decades the follicles can enter a “dormant state”, and may need reactivation.

Genetics: Just as the genes control the disease start, they also contribute to the progression and treatment outcomes. The patients will manifest differently in terms of disease severity and progression, and treatments may need to be adjusted to suit their needs. That means that a standard treatment may not be beneficial for everybody.

Autoimmune comorbidities: These are other autoimmune diseases co-existing with Alopecia Areata. The genetic predisposition for alopecia areata also predisposes other conditions such as psoriasis, vitiligo and arthritis.  That can make treatment difficult as you need to target multiple conditions. And although they have a common cause, the autoimmunity, the processes in each disease are different. For example, if a patient has psoriasis and Alopecia Areata, and treats psoriasis with drugs targeting TNFα, they will reduce severity of psoriasis but increase severity of hair loss, as this molecule is somewhat protective in Alopecia Areata.

Treatment administration: Most of the anti-inflammatory drugs can be harmful if administered for long amounts of time, and can impair lifestyles. Many patients can drop out of treatments before they are finished, or do not follow instruction correctly, which can result in inefficacy of the treatments they are receiving.

That’s very interesting Ted and one of the biggest challenges is the variance in treatment options offered by doctors for alopecia areata. How is current research contributing into furthering our understanding and developing additional treatments for Alopecia Areata?

Even with the current amount of research, many things about Alopecia Areata remain unknown. The patterns that lead to autoimmunity and hair loss are not fully understood. But a good amount of scientific research is looking into these aspects. New treatment methods are being developed and optimisation of the current ones is taking place as we are speaking. The research has not only contributed with new therapies, but also with expanding awareness for the correct diagnosis and treatment of Alopecia Areata as an autoimmune disease.

It is in the past decade or so that the research has also mapped some of the important genetic and inflammatory factors involved in Alopecia Areata.  Understanding how the genetics and environmental factor contribute to the inflammation can lead to disease prevention in the future.  As the father of medicine Hippocrates had said: prevention is better than curing. And in the following years, that can be achieved through our expanded understanding of what Alopecia Areata is.

Thank you Ted. This has been so interesting. Good luck with the rest of your project. We're looking forward to following your research journey!

The above discussion is based on Ted's full literature review which is published in the Journal of Autoimmunity. Full reference: 

Simakou, T., Butcher, J., Reid, S., Henriquez, F. (2019). Alopecia areata: A multifactorial autoimmune condition.  Journal of Autoimmunity, 98, pp. 74-85

Ted’s PhD study has received funding from Alopecia UK. We are only able to fund research projects thanks to the generosity of our regular donors and fundraisers. If you would like to support Alopecia UK with its aims of Support, Awareness and Research, please consider making a donation today.

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You can read about Ted's research project, "The application of 'Nanokicking' in immune disorders" here.