Joaquín Espinosa, PhD, executive director of the Linda Crnic Institute for Down Syndrome on the University of Colorado Anschutz Medical Campus. Also, a Professor of Pharmacology at the University of Colorado School of Medicine talks about new discoveries and treatments for individuals with Down syndrome and skin disorders.
Now what kind of skin problems do people with Down syndrome experience?
Espinosa: People with Down syndrome have higher risk of many different autoimmune conditions, including auto immune skin conditions such as atopic dermatitis, psoriasis, alopecia areata, vitiligo, and hidradenitis suppurativa.
Why is that?
Espinosa: There is an aspect of the immune system of people with Down syndrome that is always hyperactive. It’s called the interferon response. It’s the aspect of the immune system that we use to fight off viruses, but we use it only when there is a virus. Whereas people with Down syndrome activate this response constantly. And that increases the chances of autoimmunity, the immune system attacking the healthy cells.
You think about problems, but you don’t think of them being that serious, but this is?
Espinosa: Autoimmune diseases can be very painful. It can diminish the quality of life of typical people but also people with Down syndrome. Think about psoriasis for example affecting large areas of the skin, or the boils (hidradenitis suppurative) being very painful in the armpits, the groin, and other places. Alopecia areata, where their immune system attacks the hair follicle, leads to hair loss. That’s not pleasant.
So now you’re working to try to help people?
Espinosa: Yes, the scientific research that we have done at the Crnic Institute has revealed which aspect of the immune system is hyperactive in Down syndrome. We were fortunate that there are FDA approved drugs that tone down this aspect of the immune system. These drugs, JAK inhibitors, are approved for rheumatoid arthritis and other conditions in typical people. So now we will test in a clinical trial whether these drugs can be repurposed to tone down the hyper-inflammation in Down syndrome and hopefully cure those autoimmune skin disorders that are more common in Down syndrome.
How will the trial work?
Espinosa: So it is a clinical trial that involves four months of initial treatment with these FDA approved drugs to see if they are safe and efficacious in people with Down syndrome that have an active autoimmune skin condition. It could be any of the five autoimmune conditions that are more common in Down syndrome, alopecia areata, vitiligo, hidradenitis suppurativa, psoriasis or atopic dermatitis. So, if they have the skin condition, they qualify for the trial. They have to be adults, and then we’ll give them the prescription for the drug they can take for four months. In the clinical trial, we will test one of these FDA-approved JAK inhibitors, but in people with Down syndrome that have an active autoimmune condition. First of all, we want to define safety. These drugs are approved for typical people. Are they safe as well in people with Down syndrome? Then we’ll look at the efficacy in toning down the immune system and curing the skin. But then, very excitingly, we’ll see if toning down the hyper inflammation will improve cognition and quality of life in general. So those are the main goals of the clinical trial.
And those will be taken daily?
Espinosa: Yes. This is a pill they can take daily. And then if there’s a side effect with any type of concern, they can stop taking the pill, it washes off and the effect disappears very rapidly.
Is the clinical trial still open and can people around the country get in it?
Espinosa: The clinical trial is approved by the regulatory bodies and is funded by the National Institute of Health. We had to pause for three months due to the COVID-19 situation. We are ready to restart. So, we are already involved in prescreening, talking on the phone with potential participants to see if they would qualify to participate in the next few weeks. So, this class of drugs, JAK inhibitors, are showing very promising results for alopecia areata when the auto immune system attacks the hair follicle. So, what we’re seeing is that individuals that take this drug within a few weeks their hair regrows and for as long as they are on the drug the hair remains. Then if they stop taking the drug a few months later the alopecia may come back, in which case they can resume the treatment.
So, this has to feel good that you’re changing so many lives.
Espinosa: It’s very meaningful work. The research that we do in the Crnic Institute for Down syndrome has a clear potential to improve the lifestyle of people with Down syndrome. We feel very motivated, very inspired about this type of research.
Back to the drug, are there any risks you’re finding?
Espinosa: So these drugs, although they are FDA approved and found to be safe in arthritis and other conditions, are immunosuppressants so they lower the immune system a little bit. Over prolonged use, you see an increased risk of tuberculosis or infections. The relationship of these drugs to COVID-19 is very interesting. I told you that they are immune suppressants, so you would think that could increase your risk of infections. There is no data to suggest that people who are taking this JAK inhibitor for rheumatoid arthritis have more COVID-19 risk. Now interestingly, COVID-19 causes hyper-inflammation in the host, that damages the lung, the heart and other tissues. So, these JAK inhibitors are now being tested for COVID-19 to tone down the hyper-inflammation caused by the COVID virus for therapeutic purposes, including a clinical trial run by the NIAID, Dr. Anthony Fauci’s institute within the NIH.
So, this a possibly a different option then what’s being discussed now for COVID-19?
Espinosa: Correct. So, hydroxychloroquine is an arthritis drug that tones down the immune system to a degree. Now there is a reason why JAK inhibitors were developed and they are used in the clinic more than hydrochloroquine. They’re more effective at toning down the immune system and curing people with arthritis. It’s a similar story. Toning down the so-called cytokine storms, the hyper-inflammation caused by the virus, so that people don’t develop the symptoms of COVID-19. It is exactly the same drugs.
Perfect. Anything else?
Espinosa: I just want to thank all the research participants that have made this research possible to get us to this stage. And I also want to thank the Global Down Syndrome Foundation which is a key partner not only in funding the research but also in advocacy and outreach to the community.
Interview conducted by Ivanhoe Broadcast News.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
If you would like more information, please contact:
Anca Elena Call
Global Down Syndrome Foundation
(720) 548-5620
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