How the antibody blockade of IL-15 will reverse vitiligo

If you are a vitiligo patient you probably already know about the antibody blockade of il-15, also known as anti-cd122 antibody. In most vitiligo discussion forums and websites the antibody blockade of il-15 has been widely discussed for a while now. It’s what every patient is thrilled about and it is indeed, in my opinion, the most exciting subject in the vitiligo community at least for the time being. This is not surprising considering it is probably going to be the first very effective treatment in reversing vitiligo. Before we go more into details about this miracle drug that we are all waiting for, let’s start from the beginning: in summer 2018, the University of Massachussett vitiligo clinic and research lab, lead by Dr John Harris, published a significant discovery: they found that the immune system cells in the skin have a “memory”. It is after all, how it works with other viruses: once your body fights off any new harmful bacteria or virus, it then  “remembers” about it as a threat so that if the virus comes back your body will be ready to fight it off again. In vitiligo patients the melanocytes (the guys creating melanin, which gives the color to our skin) are mistakenly seen as a threat by the immune system, which “remembers” it needs to get rid of them. This is the reason why if you treat a white patch and you repigment it, once you stop the treatment it can sometimes come back to the exact same spot, even if this does not always happen. Dr Harris lab discovered that inhibiting protein IL-15 erases those resident memory cells and leads to durable repigmentation. You can read the article directly from the official website of the Umass vitiligo research lab which was published when this discovery was announced, find the article at the following link:

https://www.umassmed.edu/news/news-archives/2018/07/john-harris-lab-identifies-new-pathway-to-reverse-vitiligo/


But how does the antibody blockade of il-15 work exactly? Let’s try to describe it in simple words: imagine part of your immune system as a team of soldiers (the t-cells), if one of the soldiers spots a melanocyte , in vitiligo patients it mistakenly sees it as enemy, so it kills it and it calls all the other soldiers to kill the melanocytes around it. This is how a new white patch is formed. Now, normally the melanocytes try to come back and repopulate the region by migrating from hair follicles (which are usually not affected) as well as surrounding pigmented areas of your skin. The problem is that even if the soldiers who killed the melanocytes have left the area after their job was done, a small amount of them (the resident memory cells) remains there to act as sentinels, so that when the melanocytes come out and try to come back, these “sentinels” spot them and they signal all the other soldiers to come back and kill them again. This is why after you treat your white patch it can potentially turn white again after some time of stopping the treatment.  These “sentinels” which are left in the affected region of skin (your white patch) require protein il-15 to survive, once the anti-cd122 antibody blocks proten il-15, the sentinels are out of the picture, which means all your melanocytes are free to come back as much as they want to without anything stopping them anymore, in other words, the white patches can freely repigment.  And this is not even the good part yet! What’s even more exciting is that once the melanocytes are all back, and therefore you have repigmented, since, as we said, the sentinels are not there anymore nobody will call the soldiers to come kill the melanocytes again, therefore your vitiligo will not come back in that same patch after you have repigmented! in simple words your immune system will have “forgotten” that there was a white patch in the area, and therefore it will leave it alone. 

 


So the antibody blockade of il-15 erases the memory cells which “remember” to kill melanocyes again in that affected area of skin after you discontinue the treatment. This means that even a short time of drug administration will lead to durable repigmentation. Now, this is not a cure, but it’s pretty darn close to one because after you have repigmented you can even stop the treatment and you can be vitiligo free potentially for many years without taking the drug anymore, and yes you are not cured so you still have vitiligo, but if it shows up again at some point in your life then you will simply go through another cycle and you will be vitiligo free again for another number of years without taking any drug.

This sounds great because let’s face it, current treatments are not ideal: they require a time commitment, they are slow, and sometimes they don’t even completely work. And the only drugs which currently work effectively in reversing vitiligo like Xeljanz and Jakavi are extremely expensive and they shut down much more immune system than needed, plus, unlike the anti122 antibody they do not erase the memory cells which means if you stop taking them there is a chance your vitiligo will come back where it originally appeared. The antibody blockade of il-15 would be a complete game changer, a real treatment with minimal side effects, and you won’t even need to take the drug continuously. As much as this is incredibly exciting, there is a bad news: the fact is that clinical trials take a long time before a new drug is on the market. The antibody blockade of il-15 has been going on for years but according to Dr Harris this will be available on the market in 5 to 10 years from today assuming the trials continue to go well, so unfortunately we need to still be patient for a few years, but at least it’s something to look forward to. Another downside is that this is not a pill but it’s in form of injections, however, as we mentioned, once you have repigmented you can stop the treatment and you can be vitiligo free potentially for many years without continuing to take the drug and if the vitiligo comes back then you go through another cycle. I think a few injections for a few weeks are not such a big price to pay in order to live vitiligo free potentially for years. During testing in mice, scientists administrated it only for two weeks but they continued to see repigmentation for months to come, and because this erases the resident memory cells, your repigmentation should last a lot longer than if you were to discontinue any of the current treatments. You can also periodically go through a cycle in order to prevent vitiligo reappearing, however how often you should do that for this purpose is yet to be determined. But here is what I find to be the biggest downside of all: since not even the newest effective treatments (like the jak inhibitors) work on hands and feet very well, researchers claims it might not work in those areas, further testing needs to be done in this regard. When asked about this from someone in his blog, Dr Harris answered: “It probably won’t work on those stubborn areas (hands/feet) because those areas don’t have the hair follicles to provide the melanocyte stem cells. Still working on that problem”. However, also on the Umass university blog someone had suggested that you could have a melanocyte transplant done in the stubborn areas and then take the drug to prevent the vitiligo from coming back and Dr Harris answered that this could indeed be a potential solution. In spite of these downsides scientists really believe this will be a successful viable treatment, and with minimal side effects. 

Studies found that some autoimmune diseases share similar pathways, does this mean inhibiting protein il-15 could treat other conditions? The answer seems to be yes: Dr Harris says this could potentially treat alopecia as well, but  he said in order to know this for sure we would need to test it on a large number of patients. Also, a very similar drug which inhibits il-15 already proved to be effective in easing the effects of celiac disease. And since this already passed a clinical trial for celiac disease it at least means the drug works well on humans and it’s well tolerated. In my modest opinion this is very exciting because it gives extra hope about the success of this drug in completing the clinical trials for the treatment of vitiligo: if it already proved to be effective in celiac disease there are, I believe, more chances it will be successful in the current clinical trials for vitiligo too. In this regard we actually wrote an article about it, click here if you want to read it

I also recently found out of yet another similar drug which inhibits Il-15 (HuABC2), where pre-clinical trials showed its potential in treating type 1 diabetes as well!

This is a short but interesting audio interview with Dr Harris himself explaining the antibody blockade of il-15:

https://www.thenakedscientists.com/podcasts/short/blocking-memory-immune-cells-cures-vitiligo


You can read a couple of other articles about the antibody blockade of il-15 here.

https://www.dermatologytimes.com/article/breakthrough-vitiligo-treatment-offers-longer-lasting-results

https://medicalxpress.com/news/2018-07-treatment-disfiguring-skin-diseasevitiligo.html

and more information can be found here:

https://www.ncbi.nlm.nih.gov/pubmed/30021889


Finally, If you want to go into details there is this interesting article as well. Which, I have to warn you, is long and technical but it explains this more in depth.

https://dermatologyfoundation.org/pdf/pubs/DF_Fall_2018.pdf?fbclid=IwAR35_0VIrAC8-X6GyCzsqAkANKYxbvUWddHhFvfcSrkfTs3df7JZ9C17cNc



In conclusion, there are dozens of clinical trials for the treatment of vitiligo at the moment, more than there have ever been, but in my opinion the antibody blockade of il-15 is the most promising one at least in the near future. Unlike the jak inhibitors, this targets a more specific pathway without therefore shutting down too much of the immune system, which translates into a lot less side effects. Even if this is not a cure, the fact that you don’t need to constantly take the drug and you can be vitiligo free for potentially years after each cycle makes this drug an extremely good option while waiting for one!