The Global Down Syndrome Foundation (GLOBAL) is proud to support a
new study published in eLIFE by researchers from its
partner and Affiliate, the Linda Crnic Institute for Down Syndrome
(Crnic Institute) at the University of Colorado Anschutz Medical
Campus, that reports the initial results of a first-in-kind
clinical trial testing the safety and efficacy of a JAK inhibitor
to decrease the burden of autoimmune conditions in people with Down
syndrome. The clinical trial, which is funded by the National
Institute of Arthritis and Musculoskeletal and Skin Diseases, is
part of a portfolio of new clinical trials supported by the
National Institutes of Health INCLUDE Project.
Drawing upon their 2016 discovery that the interferon response
is constantly activated in people with Down syndrome, the team
designed the trial to focus on the autoimmune and inflammatory skin
conditions that are very common in people with Down syndrome
including alopecia areata, psoriasis, atopic dermatitis, and
hidradenitis suppurativa, and employed the JAK inhibitor
tofacitinib (marketed as XELJANZ®, Pfizer). The study also
monitored effects on co-occurring autoimmune conditions, such as
autoimmune thyroid disease, celiac disease, and arthritis.
“Individuals with Down syndrome are at a high risk of developing
autoimmune skin conditions, which are often hard to treat and cause
significant discomfort and decrease their quality of life,”
explains Dr. Emily Gurnee, assistant professor of dermatology, one
of the dermatologists involved in the study, and a principal
investigator in the trial. “Limited data exist to guide
conversations about treatment options for skin conditions common to
individuals with Down syndrome. The findings from scientists at the
Crnic Institute support the notion that JAK inhibitors are a
valuable treatment not only for skin conditions but may benefit
other autoimmune conditions prevalent in this population.”
The study team observed important improvements in skin
pathology, with the most striking results observed for those
affected by alopecia areata, as well as improvements in arthritis
and decreased biomarkers of autoimmune thyroid disease. Most study
participants chose to remain on the medicine, often through
off-label prescriptions, after completion of trial activities.
“Most importantly, we observed that major inflammatory markers
elevated in Down syndrome that are known to cause autoimmunity were
brought down to the normal range with this medicine, indicating
that the immune system is being calmed down by this JAK inhibitor,
while preserving strong immune function,” explains Dr. Joaquín
Espinosa, executive director of the Crnic Institute, professor of
pharmacology, and one of the principal investigators in the
clinical trial. “More data will be needed to define the safety
profile of JAK inhibitors in Down syndrome, and we look forward to
the completion of the trial and analysis of the full dataset.”
The study also reports the deepest characterization of the
immune system dysregulation characteristic of Down syndrome to date
through analysis of clinical data and biospecimens collected by the
ongoing Human Trisome Project study.
The Crnic Institute team analyzed clinical data and blood
samples to characterize the pattern of autoimmune conditions and
accompanying inflammatory processes in hundreds of research
participants in the Human Trisome Project using so called
multi-omics technologies. They observed that triplication of
chromosome 21, or trisomy 21, the genetic abnormality underlying
Down syndrome, leads to rapid onset of diverse autoimmune
conditions during childhood, along with increased levels of many
inflammatory factors and strong dysregulation of multiple immune
cell types.
“One key observation is that elevation of multiple inflammatory
markers and dysregulation of all branches of the immune system
occurs from a very early age, even before any clinical
manifestations of autoimmunity,” says Dr. Matthew Galbraith,
assistant research professor of pharmacology, director of the Data
Sciences Program of the Crnic Institute and co-author of the study.
“This points to a constitutive state of immune dysregulation
triggered by the extra chromosome that eventually leads to the
appearance of multiple autoimmune conditions, with variations in
timing and severity among individuals.”
“Since 2016 we have been hypothesizing that the class of
medicines known as JAK inhibitors will provide therapeutic benefits
in this population,” explains Dr. Angela Rachubinski, assistant
research professor of pediatrics, director of the Clinical and
Translational Sciences Program at the Crnic Institute, lead author
of the paper, and one of the principal investigators in the trial.
“Although JAK inhibitors have been approved for a range of
autoimmune and inflammatory conditions in the general population,
this clinical trial, which started activities back in 2020,
provides the first systematic investigation of the effects of a JAK
inhibitor in people with Down syndrome."
The Crnic Institute study team is already overseeing a second
trial testing the safety and efficacy of the JAK inhibitor relative
to other medicines for treating the condition known as Down
Syndrome Regression Disorder, and a third trial focused on children
with Down syndrome is expected to start recruitment in late
2024.
“We are very grateful to the scientists and physicians at the
Crnic Institute for their transformative research that is already
translating into improved medical care and health outcomes for the
amazing people with Down syndrome who we serve,” says Michelle Sie
Whitten, president & CEO of GLOBAL. “We are proud that GLOBAL’s
advocacy work with Congress and with the National Institutes of
Health (NIH) has led to the establishment of the trans-NIH Down
syndrome funding project, INCLUDE, that underwrites this and
numerous other groundbreaking studies and clinical trials.”
About Global Down Syndrome Foundation
The Global Down Syndrome Foundation (GLOBAL) is the largest
non-profit in the U.S. working to save lives and dramatically
improve health outcomes for people with Down syndrome. GLOBAL has
donated more than $32 million to establish the first Down syndrome
research institute supporting over 400 scientists and over 2,500
patients with Down syndrome from 33 states and 10 countries.
Working closely with Congress and the National Institutes of
Health, GLOBAL is the lead advocacy organization in the U.S. for
Down syndrome research and care. GLOBAL has a membership of over
100 Down syndrome organizations worldwide, and is part of a network
of Affiliates – the Crnic Institute for Down Syndrome,
the Sie Center for Down Syndrome, and the University of
Colorado Alzheimer’s and Cognition Center – all on the Anschutz
Medical Campus.
GLOBAL’s widely circulated medical publications
include Global Medical Care Guidelines for Adults with Down
Syndrome, Prenatal & Newborn Down Syndrome Information,
and the award-winning magazine Down Syndrome World TM.
GLOBAL also organizes the Be Beautiful Be Yourself Fashion
Show, the largest Down syndrome fundraiser in the world.
Visit globaldownsyndrome.org and follow us on social
media Facebook, X and Instagram.
About the Linda Crnic Institute for Down
Syndrome
The Linda Crnic Institute for Down Syndrome is one of the only
academic research centers fully devoted to improving the lives of
people with Down syndrome through advanced biomedical research,
spanning from basic science to translational and clinical
investigations. Founded through the generous support and
partnership of the Global Down Syndrome Foundation, the Anna and
John J. Sie Foundation, and the University of Colorado, the Crnic
Institute supports a thriving Down syndrome research program
involving over 50 research teams across four campuses on the
Colorado Front Range. To learn more, visit www.crnicinstitute.org
or follow us on Facebook and Twitter @CrnicInstitute.
About the University of Colorado Anschutz Medical
Campus
The University of Colorado Anschutz Medical Campus is a
world-class medical destination at the forefront of transformative
science, medicine, education and patient care. The
campus encompasses the University of Colorado health
professional schools, more than 60 centers and institutes, and two
nationally ranked independent hospitals - UCHealth
University of Colorado Hospital and Children's Hospital
Colorado – which see more than 2 million adult and
pediatric patient visits yearly. Innovative, interconnected and
highly collaborative, the University of Colorado Anschutz Medical
Campus delivers life-changing treatments, patient care
and professional training and conducts world-renowned research
fueled by $705 million in research grants. For more
information, visit www.cuanschutz.edu.
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- Photos provided by the Linda Crnic Institute for Down
Syndrome
Cole Wilkes
Global Down Syndrome Foundation
(720) 548-5667
cwilkes@globaldownsyndrome.org
Allison Munk
Global Down Syndrome Foundation
(720) 548-5632
Amunk@globaldownsyndrome.org