February 5, 2023

LOS ANGELES–(BUSINESS WIRE)–Children’s Hospital Los Angeles (CHLA) has initiated the first clinical trial in Down Syndrome Regression Disorder (DSRD), a rare and debilitating condition affecting adolescents and young adults with Down Syndrome.

The study — a collaboration with the University of Colorado and Children’s Hospital of Colorado — is funded by a five-year, $5.3 million grant from the National Institutes of Health (NIH) Eunice Kennedy Shriver National Institute for Child Health and Human Development . The randomized controlled trial, taking place at CHLA and Children’s Hospital Colorado, will evaluate the safety and effectiveness of three different treatments. It will also examine the role of the immune system in the disease.

“Until recently, there was no research on this condition since it was first described in 1946,” said Jonathan Santoro, MD, director of the neuroimmunology program at Children’s Hospital Los Angeles and co-principal investigator of the study. “We are excited to start this first study to advance our understanding of this condition and how best to treat it.”

An inflammatory disease?

Down syndrome regression disorder (formerly known as Down syndrome disintegration disorder) is a mysterious condition that causes previously high-functioning young people with Down syndrome to suddenly lose their ability to communicate, dress or feed, use the toilet to use or even to sleep.

“Over a period of a few weeks, these individuals lose their developmental milestones and retreat into their own world,” says Dr. Santoro. “I’ve had families tell me it’s like living with a ghost. The person is there, but not really there.”

DSRD has long been considered a psychiatric disorder or misdiagnosed as early-onset Alzheimer’s disease or late-onset autism. But there is now growing evidence that Down syndrome regression could be an inflammatory condition that could potentially be treated.

Since 2019, Dr. Santoro an experimental treatment protocol that includes high-dose steroids and an immunotherapy called intravenous immunoglobulin (IVIg). His first patient was a young man who had not spoken or moved for two years. Three weeks after his first IVIg infusion, he spoke and ran down the hall.

The Los Angeles Children’s Hospital team has now treated more than 200 patients — the most in the country. The group’s research has found that around 20% of patients with DSRD have markers of inflammation in their cerebrospinal fluid, with 85% of these patients responding to IVIg. Even patients without classic inflammatory markers respond to treatment at a rate of 70 to 75%.

It is already known that people with Down syndrome are at higher risk of developing autoimmune diseases. Still, more studies are needed to determine if DSRD is an inflammatory disease. And responses to immunotherapy aren’t always dramatic.

“The spectrum is broad, as with any disease treatment,” says Dr. Santoro. “That is why a clinical study is so important. We need to advance the science to find out which therapies are best for which patients.”

testing new treatments

The new study will enroll a total of 60 patients between the two centers, with all patients randomized to one of three therapeutic options:

  • Lorazepam, an anti-anxiety drug that treats catatonia and other symptoms

  • IVIg, an immune-regulating therapy

  • Tofacitinib, a type of drug called a JAK inhibitor that suppresses the immune system

Tofacitinib was chosen because it had previously been used successfully to treat people with Down syndrome who have other autoimmune diseases. “The JAK pathway that the drug targets is known to be dysregulated in Down syndrome,” notes Santoro. “Our hope is that this could be a more specific therapy option for DSRD.”

The study is a multidisciplinary effort between Drs. Santoro — who brings expertise in pediatric neuroimmunology and in treating the majority of DSRD patients in the country — and co-principal investigators Joaquin Espinosa, PhD, a biologist and executive director of the Linda Crnic Institute for Down Syndrome at the University of Colorado, and Elise Sannar, MD, a child psychiatrist at Children’s Hospital Colorado.

“It was a fantastic collaboration,” says Dr. Santoro. “One of the most exciting aspects is that we created this study relatively quickly. It can take 10 years for an NIH-funded clinical trial like this to get rolling. We made it in two.”

He adds that historically, people with Down syndrome have been underrepresented in research studies.

“For so long, families have been told, ‘There’s nothing we can do,'” he says. “And that is unacceptable. We have to be very scientific, but we also have to act as quickly as possible to find new treatments for these patients.”

Learn more about the CHLA Neurological Institute.

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