One of our Lay Research Panel members, Emma, has written the following blog of her thoughts about a recent webinar she attended with a talk from Professor Angela Christiano:

Having experienced alopecia areata for 15 years now, with seemingly endless visits to the GP, receiving steroid injections from the dermatologist, and much cash spent on alternative therapies; all of which have proved to be fruitless, my hope of any form of recovery has been obliterated.

As many of those with the condition well know, the effects on mental health can be absolutely devastating. And that’s how I felt. I began to fall so low, that it seemed that finding an effective treatment wasn’t a top priority, it’s ‘only hair’, and I was ‘bottom rung’ of the ladder.

This all changed for me a few weeks ago, when I was privileged to attend a seminar, presented by a true trailblazer, the eminent Professor Angela Christiano. An inspirational driver of the latest medical research into both the cause and treatment of alopecia areata, Angela is a Professor of Dermatology, as well as a Professor of Genetics and Development at Columbia University’s Irving Medical Center. The major focus of Prof Christiano's work is the study of inherited skin and hair disorders to develop genetic and cell-based therapies for skin and hair diseases.

As Professor Christiano is an alopecia patient herself, for the first time EVER, I feel somebody is genuinely and effectively fighting my corner - we’re not a lost cause! So, my hope for recovery has been reignited, and for good reason - progress is being made at pace, because of this incredible person who’s on our side.

The research is truly ground-breaking, with new depths and exciting implications to endorse further clinical trials and treatment in the UK. The key take- home messages from the seminar were:

• There was originally a bias that assumed alopecia areata would have most in common with other skin inflammatory conditions. But starting with genetics studies a decade ago, Christiano showed that alopecia areata involves pathways which have more in common with rheumatoid arthritis, coeliac disease and type 1 diabetes, than with inflammatory skin conditions such as eczema and psoriasis. I wonder if this could have implications in the way that alopecia areata is viewed and treated in the UK. It strengthens the case for specialities to work together and share knowledge and make collaborative decisions as treatments become available. We see this already in rheumatology, gastroenterology, and paediatrics, when treating patients with other inflammatory diseases.
• Secondly, with no JAK inhibitor yet licenced in the UK for the treatment of alopecia areata, many people are driven to extreme lengths to access JAK inhibitors such as Xeljanz (tofacitinib). Christiano’s more recent research paves the way for the development of a new generation of JAK inhibitors, which are more targeted. Her studies in a strain of mice that naturally develops alopecia, show that treatment with just a JAK3 inhibitor alone, or a JAK1 inhibitor alone, was sufficient to reverse alopecia and reduce inflammation in the skin, but that JAK2 inhibition was not required. For me, this was a revelation with far-reaching implications for the use of the current first generation of pan-JAK inhibitors such as tofacitinib (which targets all the JAKs), if the same were found to be true in humans. We are waiting to hear more details of the clinical trials now taking place, but hopefully these more narrowly selective JAK inhibitors may become the drugs of choice for dermatologists to prescribe. We can hope that further clinical studies in people will get us closer to a more refined approach to reversing alopecia areata with JAK inhibitors, and that the prospect of licensing JAK inhibitors is gaining momentum in Europe and the UK.
• For the one-third of non-responders to JAK inhibitors, Professor Christiano's research does not ignore these patients. The studies extend to showing that white blood cells called CD8 T cells move from blood vessels in the skin into the innermost part of the hair follicle where they destroy hair producing cells. This opens the possibility of using new small molecule inhibitor drugs aimed at the signals that T cells depend on to do their damage. There is already a drug which can block a protein called LFA-1, which guides T cells in the skin and makes them competent to target the hair follicle. This drug is approved as a topical treatment for dry eye disease, and more investigations are needed to test in in alopecia in the future.
• The research is also moving closer to identifying a trigger of alopecia areata. This provides huge empowerment to those with the condition and has personally had a huge impact on my mental health. It was interesting to hear that a single gene, for a type of keratin in hair called KRT82, is associated with alopecia areata, and it does not seem to be responsible for pitted/weak nails. This is a revelation as so many people link them together. This is an important development that shines new light on previous studies from several years ago that keratins may be the elusive autoantigen for alopecia – at least for some patients - and provides a focus for further investigation. Conversely, it may turn out that there are many other genes involved, and we await further research to help reveal their different roles.
• Finally, I was heartened to hear that Professor Christiano’s next goal is to investigate long-term reversal of alopecia areata. Currently many patients experience flares once treatment with JAK inhibitors is stopped. Christiano’s team have shown that some of the T cells which invade the hair follicle remain there during treatment, as ‘resident memory T cells’. These are ‘the enemy’ in Christiano’s words, which could explain the recurrence of alopecia when treatment stops. It’s a challenging area but being investigated nonetheless to find ways to block these cells using single-cell ‘barcodes’ of their unique T cell receptors. Certainly, next stages will focus on both the ongoing immune response, as well as protecting the integrity of the subsequent hair follicle.

There is no doubt that, because of the dedication and ground-breaking work of Professor Christiano, it is reality that we are moving closer to a long-term cure for alopecia areata. It is a comfort to know that such a distinguished scientist, who knows first-hand what it’s like to have alopecia, is championing these studies and being such a brilliant advocate.

The future looks brighter again because of this wonderful person – I’m so pleased to have been invited to attend the seminar!

Thanks so much to Emma for being a member of our Lay Panel and for sharing her thoughts with us.