Global Webinar Series – Spring 2018 Recap

 SPRING 2018

An Unprecedented and Exciting Down Syndrome Research Discovery Engine – The Crnic Institute Human Trisome Project

What You Need to Know



Overview & Speaker:


This webinar provides you important information, in layman’s terms, about the Crnic Institute Human Trisome Project – one of the most exciting Down syndrome research projects that aims to improve the health of children and adults with Down syndrome and millions of others who are affected by autoimmune diseases, Alzheimer’s, and cancer. Learn about new discoveries that recast Down syndrome as an immune system disorder and learn how self-advocates and local Down syndrome organizations can support this important effort.

Dr. Joaquín Espinosa, PhD
Executive Director, Linda Crnic Institute for Down Syndrome, CO

Dr. Joaquín Espinosa is the Executive Director for Science at the Linda Crnic Institute for Down Syndrome. He is also a Professor in the Department of Pharmacology at the University of Colorado Denver School of Medicine, the co-Leader of the Molecular Oncology program at the University of Colorado Cancer Center, and the founding Director of the Functional Genomics Facility at the University of Colorado.

Overview: Click to View

Powerpoint Handout: Click to Download



Veronica in Albuquerque, NM:

1. Out of nowhere, my daughter had a “psychotic” episode a few years ago that lasted 3 years. It looked like regression, but during that time she was vulnerable to every kind of infection and autoimmune disorder, never actually diagnosed. How do you think this is explained?

It is hard to provide an explanation, or even a hypothesis, without more information, but this is a tantalizing connection between a neurological event and immune-related events. The research described at the webinar showing constitutive activation of Interferon signaling in people with Down syndrome predicts that stimuli that activate Interferon signaling, like a viral infection, would produce an exacerbated immune response, with myriad potential negative consequences, such as the sudden onset of an autoimmune condition or neurological dysfunction caused by hyper activation of microglia, the immune cells in the brain. This hypothesis is currently being tested by ongoing research.

2.How can we be part of this research?

Please contact research coordinators for the Crnic Institute’s Human Trisome Project via


Karen in Ancaster, Ontario:

1. If I boost my son’s immunity with things like a whole food diet, proper sleep, vitamin D, Echinacea, elderberry syrup, etc. will that help increase his muscle tone and brain function more than it would a typically developing child?

There has not been a comparative clinical study to provide a definitive answer to this question. Nevertheless, a whole food diet and proper sleep are beneficial to us all.

2. Based on this new breakthrough, is there anything I should do to improve my child’s life and allow him to thrive?

It is recommended that special attention be paid to any health events that could be linked to immune dysregulation and their potential ramifications. A greater emphasis on the immune system during clinical consultations is recommended, including a consultation with an immunologist if possible.

3. How would this information be distributed in the medical field? Will it be taught in Medical School? Or should I be the one to spread the word to my doctors in order to get them to hopefully look it up?

Scientific results are published in peer-reviewed journals and discussed at myriad conferences at the national and international level attended by researchers and clinicians. The Global Down Syndrome Foundation has also promoted these scientific results though Roundtables at the National Down Syndrome Congress Annual Convention and the annual conference of the Down Syndrome Affiliates in Action Leadership Conference. Nevertheless, it is advised that this research be brought up to the attention of the doctors providing medical care to raise awareness about the role of the immune system in Down syndrome.


Brad in Colleyville, TX:

1. Has there been any consideration to looking at herbs or supplements that might influence interferon levels or receptor sensitivity?

There is some published literature showing that some natural compounds can inhibit Interferon signaling in cell culture and mice, such as curcumin and compounds in Chinese skullcap extracts, but there is no definitive clinical trial to determine the therapeutic benefit of these compounds in Down syndrome.


Gail in Dover, DE:

1. Can medical conditions such as Kwashiorkor, FPIES, and GI issues be related to your research too? For example: an individual with DS also being diagnosed Kwashiorkor, FPIES, Gastroparesis, and Autism?

There is no research establishing a clear link between Interferon signaling and Kwashiorkor and FPIES. However, there is a strong link between celiac disease and Interferon signaling (see Bouziat et al, Science 2017). Ongoing research efforts at the Crnic Institute are aimed at elucidating the role of Interferon signaling in the increased prevalence of celiac disease and autism in people with Down syndrome, as well as studies of the gut microbiome. 

2. Are you looking for more research patients for upcoming studies? If so, what qualifications are you looking for to accept them?

Yes, we are looking for more participants, and no special qualifications are required. Please contact research coordinators for the Crnic Institute’s Human Trisome Project via

3. What can we do to support the immune system to lessen medical issues for those individuals with DS?

Ongoing research at the Crnic Institute is aimed at defining safe and effective therapeutic strategies to normalize the immune system in people with Down syndrome. Until such strategy is tested in clinical trials and approved, the only recommendation is to bring this research to the attention of the doctors providing medical care to raise awareness about the role of the immune system in Down syndrome.


 Emily in St. Louis, MO:

1. Are there any drugs to address anxiety/depression in the Down syndrome population that have been found to be more effective than others?

There hasn’t been any research done on what medications are more effective than others.  There are certain prescribing practices that psychiatrists have, but this can vary. *Answer provided by Dr. Lina Patel, Director of Psychology at the Sie Center for Down Syndrome.

2. Are there different therapeutic doses for this population as compared to the general population?

Kids with developmental disabilities tend to do well on lower doses, but again, it varies from child to child, as they are all so different.  Working with someone who is well versed in developmental disabilities is the key. *Answer provided by Dr. Lina Patel.

3. Is there any research recommending best practices for managing the process for your loved one with DS?

Please consult medical guidelines for children with Down syndrome here. The Global Down Syndrome Foundation is currently working on establishing similar guidelines for adults with Down syndrome.
Downloadable record sheet here.


Wendy in Eagle River, AK:

1. Will you be looking at any of the new research that suggests links between gut bacteria and autoimmune diseases?

Yes, researchers at the Crnic Institute are currently investigating the oral and gut microbiome in people with Down syndrome. 

2. There are a few articles on NCBI that suggest autoimmune diets improve clinical symptoms of autoimmune diseases-will that body of research influence where you look next?

This question may be referring to ‘anti-inflammatory diets’. We are indeed following this body of literature to inform the research at the Crnic Institute.

3. Is there anything parents of infants with Down syndrome can do with your research results yet or is it a sit and wait game?

The only recommendation at this point is to bring this research to the attention of the doctors providing medical care to raise awareness about the role of the immune system in Down syndrome.


Suzanne in Monument, CO:

1. We know our population is more susceptible to celiac disease. Would it be sensible to recommend adding a genetic test for HLA DQ2 and DQ8? Obviously families, whose children have neither gene can be comforted knowing their child will not develop celiac disease and those that test positive can make dietary changes to potentially avoid their child developing this auto-immune condition.

Yes, it is sensible to do these tests, but the presence of predisposing DQ2 and DQ8 alleles does not guarantee the development of celiac disease (and their absence does not guarantee that a person will not develop celiac disease). These genetic tests inform about ‘relative risk’ of developing celiac, and are by no means definitive diagnostic tools.


Robbin in Pewaukee, WI:

1. How can Down syndrome organizations in other states help with the Human Trisome Project?

You can advertise the project in your community. Please make your community aware of the information at

2. What ways can we support the research you are doing?

By raising awareness about the research results, advertising and participating in the Crnic Institute’s Human Trisome Project, and through donations to the Global Down Syndrome Foundation.


Sandra in Carol Springs, FL:

1. What will the main changes on our children with Down syndrome be from your discovery?

The full impact of the discoveries is yet to be defined, but it is possible to envision that the ongoing research could illuminate ways to modulate the immune system for therapeutic purposes.

2. The immune system is affecting those with Down syndrome and affecting their cognitive abilities. Could this have been confused with depression?

It is known that treating typical people with Interferons can cause depression as a side effect, so it is possible that hyper activation of Interferon signaling in people with Down syndrome can cause depression-like symptoms.

3. How can we move forward to make changes or approach how their immune systems are affected?

The only recommendation at this point is to bring this research to the attention of the doctors providing medical care to raise awareness about the role of the immune system in Down syndrome.

4. How is it that my son was a competitive athlete, on correct diet, great health, no sleeping problems, and his immune system has provoked his regression?

We do not have a good understanding of the molecular and cellular underpinnings of regression, and we are actively developing research protocols to investigate if regression is linked to sudden episodes of immune dysregulation, such as a viral infection.


Kathleen in Colorado Springs, CO:

1. I have heard that people with Rheumatoid Arthritis don’t get Alzheimer’s. Why would Rheumatoid Arthritis be one of the autoimmune diseases that people with DS have?

This is an interesting observation that is being investigated at the Crnic Institute in collaboration with Dr. Huntington Potter. Dr. Potter has investigated why people with RA have lower rates of Alzheimer’s and identified the immune-modulatory molecule known as GM-CSF as the potential culprit. GM-CSF is elevated in people with RA and Dr. Potter’s team showed that GM-CSF can reverse Alzheimer’s pathology in animal models. His team is currently testing the therapeutic benefits of GM-CSF in clinical trials in typical people with early signs of Alzheimer’s, and we are currently collaborating to understand the interplay between Interferon signaling and GM-CSF in Alzheimer’s in people with Down syndrome. Of note, GM-CSF is not elevated in people with Down syndrome. On the other hand, we know that RA is driven by inflammatory cytokines, such as TNFa, which are elevated in people with Down syndrome, most likely because of too much interferon signaling. Thus, it all comes down to the balanced activity of diverse immune factors with varied effects on Alzheimer’s and RA.

2. Are you still taking participants for the study? How do you enroll?

Please contact research coordinators for the Crnic Institute’s Human Trisome Project via

3. My friend has Down syndrome with multiple immunological issues – Type 1 diabetes, hypothyroidism, adrenal dysfunction. Can these diseases be made better with some of the medications that are available today?

Each of these conditions is currently being treated with different approaches, such as hormone supplementation for hypothyroidism. Ongoing studies at the Crnic Institute are investigating whether all these autoimmune conditions could be driven by a common molecular and cellular root involving the Interferon pathway.


Kathleen in Vienna, VA:

1. Can you describe the sample of 300 individuals that are in the study: age, gender, and other variables?

Currently the Human Trisome Project has enrolled >340 participants, ~180 of them with Down syndrome, both genders, ages 6 months to >70 years old.

2. Any preliminary results from the drugs? And how do you test drug outcomes with control groups?

Research efforts with drugs that inhibit Interferon signaling are currently underway.


Suzanne in Monument, CO:

1. Is taking a diet inventory part of this process to see if there is a significant impact of diet on those participants? (i.e. less immune response and low inflammatory diet)

Participants in the Crnic Institute’s Human Trisome Project provide information on diet and dietary supplements, which could potentially reveal links between diet and various degrees of immune dysregulation.

2. How would a family know if their child is impacted by high interferon impacts? Is there a simple blood test?

There is no simple blood test for Interferon signaling, but it is measured in all participants in the Crnic Institute’s Human Trisome Project.


Julie in Highlands Ranch, CO:

1. During your evaluation of the samples, is it possible that you could stumble upon a possible disease process happening for a donor? If so, would you contact that individual to inform them?

Yes, such occurrence is possible, in which case the participant would be contacted to be informed about the event.


Wendy in Port Townsend, WA:

1. Is it possible/what would it take to collect samples from local populations and send them in for the Human Trisome Project?

The research team has already collected samples at remote collections, and is currently exploring ways to organize more remote collection events.

2. Would long term immunosuppression be a potential generalized treatment option? Like in the case of rheumatoid arthritis and methotrexate?

Ongoing research is aimed at defining the potential therapeutic benefits and safety of immune-modulatory strategies in Down syndrome.

3. If we attend a Down syndrome clinic visit with Dr. Hickey, could we add an immunologist appointment to the team approach? When we visited last year we were not offered entry to the Human Trisome Project–could that be changed with visits to Dr. Hickey and team?  If we enter the project, can we see our child’s results?

Please consult with Dr. Hickey about an appointment with an immunologist and inquire about the Human Trisome Project. Dr. Hickey is a member of the HTP team and would happily facilitate consent and sample collection. Depending on what time exactly last year you visited, consent at the Sie Center may not have been in place at the time, but it is now. Results are not returned to participants, unless there is an ongoing medical condition that the participant needs to be made aware of.


Christina in Scarborough, Ontario:

1. In line with the observations of upregulated IFN receptors, is there any evidence for enhanced (more robust) antiviral responses in DS, and do you plan to look at this in future? Do you plan to look at cellular responses in future, or just observational/descriptive studies?

It is well established that cells of people with Down syndrome have an enhanced anti-viral response in culture, but little is known about the strength of the anti-viral response in living individuals with Down syndrome, which is a topic of intense research at the Crnic Institute.

2. You showed elevated cytokines (IL-6 and TNF-alpha), but did not comment on IFNs (ligands)? Any enhanced production of IFN-alpha or IFN-beta observed?

It is well established that people with Down syndrome have elevated levels of circulating IFN-gamma ligand. Studies of –alpha and –beta ligands are currently underway.


Patricia in North Vancouver, British Columbia:

1. Are there any updates on the use of minocycline to reduce inflammation (and could Apprilon be a better tolerated drug with same anti-inflammatory properties)?

Minocycline was tested in animal models of Down syndrome and shown to be beneficial in the mouse models. Definitive clinical trials for the use of minocycline or apprilon have not been completed in people with Down syndrome.

2. Could you please share the list of research articles you have reviewed with regard to supplements and diet to reduce inflammation?

Not really by this medium, it is hundreds of articles you are referring to.

3. Do you know anything about Longvida Curcumin?

There are more than 100 clinical trials for curcumin for diverse conditions and there is some evidence that curcumin can attenuate Interferon signaling in some settings, so I am following these clinical trials with much interest.


Beatriz in Lexington, KY:

1. Any study on vit D3 related to the immune system?

Yes, there are many studies, too many to list here. Please consult the Pubmed library for more information.


Veronica in Albuquerque, NM:

1. How can we participate in the project? I have a 29-year old daughter.

Yes you can. Please contact research coordinators for the Crnic Institute’s Human Trisome Project via


Dawn in Salida, CO:

1. Oncology is using genetic testing to match patients to most effective treatment. Would it be beneficial for individuals with DS to be tested for these levels of inflammatory proteins, interferons, etc. so therapy can match what is really going on?

This is an excellent question very much in line with the ongoing research. We are currently working to identify which inflammatory proteins could serve as ‘biomarkers’ to predict specific co-morbidities in the population with Down syndrome.


Deborah in Santa Fe, NM:

1. In cancer patients, IL-6, TNF and VEGF are often elevated, how do DS people, who have these elevated escape getting cancer?

In cancer patients, these elevated levels would be caused by an immune response to the tumor. In people with Down syndrome, these would be caused by elevated Interferon signaling. Of note, Interferon signaling is known to slow down tumor development.

2. Will you be looking at the various autoimmune antibodies? (Cyrex Labs seems to have the most comprehensive panels)

Yes, we are currently investigating a plethora of autoimmune antibodies as part of the Crnic Institute’s Human Trisome Project.


Marcy in Littleton, CO:

1. Any recommendations for caretakers of individuals with Down syndrome based on the findings thus far?

The only recommendation at this point is to pay special attention to events that could be indicative of strong immune dysregulation, and to bring these events to the attention of the medical care providers to raise awareness of the importance of the immune system in Down syndrome.


Laura in San Ramon, CA:

1. Are you saying people with DS have weak immune systems or over active immune systems?

We talk about immune dysregulation, with some aspects of the immune system being hyperactive (e.g. anti-tumoral responses), while others being weakened (e.g. anti-bacterial responses).

2. What about proteins? Like people with autism, are they unable to digest proteins?

People with Down syndrome can digest proteins alright, but recent studies show differences in amino acid metabolism in people with Down syndrome.

3. We have family in Colorado Springs. Where is the lab we can stop in to give samples while we’re there?

Currently, there is no active sample collection site at Colorado Springs. Please contact research coordinators via to arrange sample collection if you are in Denver.


Kaycee in Great Falls, MT:

1. Could you please share the article or information on the herbs you mentioned that have been shown to have an anti-inflammatory effect?

Too many to list here. Please search in Pubmed for ‘curcumin + Interferon’ and ‘chinese skullcap + interferon’.


Susan in Fairfax, VA:

1. One point that you made during the presentation was about the autoimmune process being activated without a trigger. In my son’s case, I believe there was a trigger. What might be the most significant difference?

We hypothesize that bacterial and viral infections, or other types of strong immune-activating stimuli, could enhance the likelihood of triggering an autoimmune condition in Down syndrome, but his hypothesis has not been tested yet.

2. In August of 2008, my son with DS, then 17 years old began vomiting relentlessly every day, much of which was clear liquid. I was in the GI office 2-3 times per week when my son was misdiagnosed with constipation. In January of 2009, the gastroenterologist finally did an endoscopy and discovered the obstructive pyloric channel and dilated it. A week later the dilation failed and had to be re-dilated. At that point, I pulled my son out of school and he began a road to recovery. We hired an attorney to deal with the school system and two years later my son returned to a different high school with an improved IEP. However, once back in the school system, he began to not do so well. Apparently stress is a histamine trigger and my son has a significant and very rare vision impairment (unilateral aphakia with amblyopia in his phakic eye) that the school system had no idea or will to accommodate properly. I have lost count of how many dilation endoscopies he has had since then. This past year, July 2016 was the worst. The new gastroenterologist was afraid to dilate for fear of tearing the tissue and was recommending vagotomy which I resisted. I noticed that when I gave the PPI drug, my son’s GI symptoms actually became worse. I had to dig deep to figure out what was going wrong. We looked at the low histamine diet as well as enzymes for digestion and both of those seemed to help enormously to get past this crisis. We work with functional medicine physician, Norm Schwartz, to evaluate my son’s health. We are evaluating Joseph for Chronic Inflammatory Response Syndrome – possibly as the result of exposure to environmental mold and mold toxins, this is a matter of deep concern. So I am trying to formulate a question from all of this: how can a unique genetic profile alter the impact of interferon? I want to prevent my son from ever having another episode of obstruction because it could have dire consequences for him. I have to work really hard to accommodate all of his needs and to reduce his stress as well as manage his diet. I am deeply concerned that should something happen to me or my husband that most folks will not be able to address his needs. He does now take a xymogen probiotic ProBioMax 350 that has helped him quite a bit. But right now he is spending his days mostly at home to be close to the bathroom as well as to avoid exposure to environmental molds. Any thoughts or suggestions?

It is clear that you have been a very strong advocate for your son’s health and have taken necessary steps to evaluate his degree of immune dysregulation and potential drivers of specific symptoms. I have no specific suggestions beyond words of encouragement and support as you work with Dr. Schwartz and other physicians.


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