This new study, which will be funded over five years by a $5.3 million grant from the Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD), is a first-in-kind holistic investigation into the potential causes of DSRD as well as promising therapeutic approaches for this debilitating condition affecting a small but growing percentage of adolescents and young adults with Down syndrome. The multidisciplinary team is led by Dr. Joaquín Espinosa, executive director of the Crnic Institute, Dr. Elise Sannar, assistant professor of psychiatry at CHCO, and Dr. Jonathan D. Santoro, director of neuroimmunology and assistant professor of neurology and pediatrics at CHLA and the Keck School of Medicine at the University of Southern California. The Crnic Institute is an affiliate organization of the Global Down Syndrome Foundation (GLOBAL) and the largest center for Down syndrome research in the world.

DSRD is a severe neurological condition with symptoms such as acute loss of speech, inability to perform activities of daily life, catatonia, hallucinations, delusions, depersonalization, insomnia, and aggression. Although rare, adolescents and young adults with Down syndrome seem to be at higher risk for this condition.

Lina Patel, PsyD, associate professor of psychiatry at the University of Colorado School of Medicine, and member of the Crnic Institute research team says, “DSRD is often described as a condition whereby a person withdraws into their own inner world. Many common daily activities are suddenly disrupted, such as going to the bathroom, eating, communicating with others – it all goes away suddenly and they lose a lot of the skills they’ve gained over the course of their life.”

Eileen Quinn, MD, is an associate professor of pediatrics at the University of Toledo College of Medicine and Life Sciences and manages a Facebook group for families and medical professionals searching for answers about DSRD. She started the group after her own daughter Sara, who has Down syndrome, began showing signs of regression.

“I was terrified, because I could tell what it was, and I knew there were no good answers.”

Before experiencing regression, an evaluation from Sara’s elementary teacher read, ‘Sara has a sparkly personality’ and, ‘many friends who want to spend time with her.’ But, after starting middle school, Sara suddenly became withdrawn, unable to make eye contact and developed repetitive, ritualistic behaviors among other symptoms.

“To lose her like that, so abruptly and completely… it was just horrible,” says Quinn.

According to Quinn, it has taken years of seeking treatment and trying numerous medications and therapies to see some improvement, but she believes Sara is not as capable as she could be with more effective treatments.

It is stories like Sara’s that inspired this multidisciplinary research team to develop an ambitious study of the causes and potential treatments for DSRD.

Currently, the true cause of DSRD is unknown. Until recently, it was considered a strictly psychiatric condition and was often misdiagnosed as more common conditions such as autism spectrum disorder (ASD) or early-onset Alzheimer’s disease in people with Down syndrome. However, emerging research from CHCO and CHLA has revealed a possible immune mechanism in some patients.

“A growing body of evidence is pointing to dysregulation of the immune system as a possible mechanism underlying DSRD,” says Dr. Espinosa. “Research at the Crnic Institute has shown that individuals with Down syndrome experience chronic hyper-inflammation throughout their lifetimes and are highly predisposed to develop autoimmune conditions. In many ways, DSRD resembles neurological conditions where the immune system attacks the brain, such as autoimmune encephalitis.”

This new research study will focus on investigating the role of the immune system in DSRD as well as comparing current treatments to find the most effective option. To do this, the team will conduct a research-intensive clinical trial to compare the safety and efficacy of three alternative therapeutic approaches: two promising immune-modulatory medicines, intravenous immunoglobulin (IVIg) and the JAK inhibitor tofacitinib (also known as Xeljanz), and the psychiatric drug Lorazepam, a benzodiazepine used to treat catatonia and other symptoms of DSRD.

Dr. Santoro, a trained neuroimmunologist and leading expert in the clinical management of DSRD, has seen promising results treating the condition with multiple immuno-modulatory medicines, especially in those with patients who present diagnostic abnormalities indicative of inflammation affecting the brain.

“We have seen patients with Down syndrome who had not spoken or moved in two or three years start running down the hall and speaking within weeks of treatment,” said Santoro.“It has completely changed our understanding and treatment of DSRD.”

“This is an important study that will compare three different treatments acting through diverse mechanisms and which will directly test the hypothesis that immune dysregulation underlies many cases of DSRD,” Dr. Sannar added.

“We are so pleased that GLOBAL’s advocacy work with our self-advocates, Congressional Champions and NIH has led to the establishment of INCLUDE, the trans-NIH Down syndrome research project,” says Michelle Sie Whitten, President & CEO of GLOBAL. “INCLUDE-funded clinical trials specifically for people with Down syndrome, such as the DSRD study, have led to a renaissance in Down syndrome research and care. We are deeply grateful to our scientists, NIH and our amazing Down syndrome community for investing in GLOBAL’s work to elongate life and improve health outcomes.”