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New Down Syndrome Study Goes Beyond Skin Deep

Researchers hope drug trial turns corner in genetic disorder

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Written by Debra Melani on March 18, 2020

Patchy bald spots and painful skin lesions are targets of a new clinical trial aimed at curbing common skin conditions in people living with Down syndrome. For trial participants, that success would be benefit enough.

But for researchers at the Linda Crnic Institute for Down Syndrome on the University of Colorado Anschutz Medical Campus, the aim goes far beyond the body’s outer layer.

Led by Executive Director Joaquin Espinosa, PhD, the research into the safety and efficacy of a drug called tofacitinib could provide a groundbreaking path toward solving chronic immune system dysregulation and its deleterious impacts in the population with Down syndrome.

Drug shows promise with skin disease and more

“These conditions can really decrease quality of life, such as the condition known as hidradenitis suppurativa,” Espinosa said of the immune-driven skin disorders that unequally strike people with Down syndrome. This chronic condition (more commonly known as acne inversa) causes inflamed, pus-filled lumps that often break. “It can be very painful and very difficult to treat,” Espinosa said.

World Down Syndrome Day

Although the annual celebration at the Colorado State Capitol was cancelled due to the COVID-19 threat, Saturday (March 21, in recognition of the triplication of chromosome 21, or trisomy 21) is World Down Syndrome Day. Launched in 2012 to celebrate the growing Down syndrome population, 190 countries recognize the day. About 6,000 babies are born with the chief chromosomal disorder in the U.S. each year. Between 1979 and 2003, the number of babies born with Down syndrome increased by about 30% (Centers for Disease Control and Prevention).


Other related skin conditions common in patients with Down syndrome, the most common chromosomal disorder in humans, also include alopecia areata (autoimmune baldness), atopic dermatitis, psoriasis and vitiligo (blotchy loss of skin color).


Joaquin Espinosa chats with a family at last year's World Down Syndrome Day at the Colorado State Capitol. The event was sponsored by the Global Down Syndrome Foundation.

“This trial shows tremendous promise in treating these conditions,” said Espinosa, whose team has been following two patients being treated with tofacitinib for alopecia areata with tremendous hair-regrowth success. The drug is already FDA-approved for rheumatoid and psoriatic arthritis.

But Espinosa’s team will also look at whether the drug will normalize biomarkers of immune dysregulation, potentially improving many health outcomes in individuals with Down syndrome, such as other autoimmune disorders or even perhaps cognitive function.

Immune system overdrive: ‘not a good thing’

“A few years ago, we discovered that people with Down syndrome have chronically activated interferon signaling,” Espinosa said of a branch of the immune system involved in fighting off viral infections. The groundbreaking research was published in eLife in 2016.

Using today’s COVID-19 pandemic as an example, Espinosa said having the inflammatory response in constant overdrive can be deadly.

“Most of the mortality associated with the COVID-19 virus is caused by the immune system going into overdrive, eventually causing severe respiratory distress and failure of other organs. Having an excessive immune response is never a good thing. And when you understand the immune system and its potential impacts on development, you realize that a lot of what we know about Down syndrome could be driven by this consistent, constant dysregulation of the immune system.”

People with Down syndrome have more complicated reactions and hospitalizations with some respiratory diseases, such as RSV (respiratory syncytial virus) and H1N1 (influenza subtype associated with the 1918 Spanish flu), Espinosa said. But the novel coronavirus disrupting the world today remains too new to define its impacts on people with Down syndrome, he said.

For more information on the clinical trial, email dsresearch@ucdenver.edu


Born with an extra copy of chromosome 21 (trisomy 21), the condition strongly predisposes people with Down syndrome to numerous health issues, including leukemia, Alzheimer’s, thyroid dysfunction, celiac disease and diverse neurological and autoimmune diseases. Due to improved medical care, the life expectancy for people with Down syndrome has increased dramatically in the last five decades, and newborns with Down syndrome today are expected to live into their 60s.

Blocking a pathway of widespread disruption

Tofacitinib, an immunosuppressive drug, inhibits key proteins in the interferon pathway called Janus kinases (or JAKs), Espinosa said. Supported by scientific evidence showing that JAKs are key mediators of immune dysregulation in people with Down syndrome, the researchers hope the drug might normalize widespread immune dysregulation, positively influencing many aspects of health in the population.

Espinosa hopes the four-month trial results warrant more, longer-term studies.

“Chronic inflammation is a bad thing to anybody, with or without Down syndrome. And with Down Syndrome, it is through the roof,” Espinosa said. “If we can normalize the immune system even to a degree, it is predicted that there will be multidimensional lifelong benefits.”