Barrier dysfunction and blood inflammation associated with Down syndrome regression disorder

A new study conducted by Jonathan D. Santoro, MD, director of the neuroimmunology program at the Los Angeles Children’s Hospital, shows evidence of the dysfunction of the brain barrier and inflammation in the central nervous system in people with Down syndrome regression disorder (DSRD).

The new study, “CSF Immunoglobulin’s Immunoglobulin dysfunction in Down syndrome was published in February 25, 2025. It was led by Dr. Santoro in cooperation with Saba Jafarpour, MD, Natalie K. Boyd, Benjamin N. Vogel, Lina Nguyen and Lilia, Lilia Lilia, Lilia, I Lilia, Lilia, I Lilia, I Lilia, Lilia, and Lilia, Lilia, I Lilia, Lilia, and Lilia. Chla Neurological Institute. The team worked closely with Linda Crnni Institute at the University of Colorado and its director, dr. Joaquin Espinos.

This is a huge missing element in the puzzle of what we know about the regression disorder of Down syndrome. “

Dr Jonathan D. Santoro, MD, director of the neuroimmunology program, children’s hospital Los Angeles

Leading DSRD research efforts

Over the past few years, Dr. Santoro, Dr. Jafarpour and their team in strategic therapies of overcoming reactive immunology (Storm) conduct several research activities and develop new DSRD treatment. This rare, but more and more diagnosed state causes a quick decrease in young people with Down syndrome. People with high functioning will violently lose their ability to communicate, feed, sleep, dress or use the bathroom. Some people with disorder become still and catatonic.

Although DSRD was first described in the article in 1946, it was not widely examined, because many assumed that it was a mental state or potentially early Alzheimer’s disease, which are well described in this population. But the team of Dr. Santoro began to meet with DSRD patients and continued to study it. Their early research identified inflammatory markers in the cerebrospinal fluid of patients, which indicates that DSRD can actually be inflammation affecting the brain. “It was Aha’s moment,” says Dr. Santoro.

This discovery informed Dr. Santoro’s treatment for DSRD and began to administer high dose steroids, as well as immune therapy called intravenous immunoglobin (IVIG). This approach turned out to be highly effective, enabling patients to regain the ability to walk, run and communicate.

But clinical trials identified cerebrospinal fluid abnormalities, which indicate neuroin inflammation only in the faction of DSRD patients, which was not associated with a high indicator of success immunotherapy Among this population. The team of Dr. Santoro and their colleagues from the University of Colorado continued their in -depth research.

New DSRD evidence as inflammation

In the last study he finds clear evidence that DSRD is indeed inflammation. It also combines DSRD with a blood-brain barrier dysfunction, a layer of cells that form a membrane between blood and brain to filter harmful substances. “Blood-brain barriers are of key importance for maintaining the immune system in front of the brain,” says Dr. Santoro. “Any interference may be enough to cause a neurological disease.”

In the new study, it included samples of cerebrospinal fluid from three different patients’ populations: people with DSRD, people with a known neuroimmune or neuroinomal condition, such as multiple sclerosis or autoimmune encephalitis and neurotypical, and control non-engineering.

Proteomic profiling of samples from these people allowed researchers to examine the proteins found. Metabolomic profiling identified metabolites-chicks created when food, medicines, chemicals or tissue are broken down-and enabled scientists to identify the functional status of cells in the body. And the profiling of immune markers analyzed specific particles expressed by immune cells in samples.

Indications of inflammation and disorders of the blood-brain barrier

The data showed increased dilution in proteomic signatures in DSRD samples and neuroinomyzia compared to healthy control patient samples, especially the regulation of several sequences of immunoglobulins, which indicate neuroic. In addition, patient samples from DSRD showed significant regulation up to the proteins of erythrocytes and plasma proteins from the liver, which indicate the poor integrity of the blood-brain barrier. The immune marker profile of the DSRD patient samples was also similar to various other neuroimmune conditions.

Based on these results, Dr. Santoro and his team have determined that the cerebrospinal fluid of people with DSRD has proteo and metabolic signatures that comply with both neuroin inflammation and the increased permeability of the blood-brain barrier.

“Proteomic irregularities found in this study confirm what we have seen in clinical practice – the immune system is the main player in DSRD,” says Dr. Santoro.

The cerebrospinal fluid of patients with DSRD is also more comparable to patients with neuroinase disorders than for healthy control patients, which suggests a potential cause of DSRD associated with immunity, which can affect future treatment strategies.

“The implications of these findings are deep and I hope that it will be the next step to find the cause of DSRD,” explains Dr. Santoro.

The study led to the clinical trial phase IIb assessing safety and effectiveness Immunotherapy in people with DSRD. This clinical examination, conducted at the Linda Crnic Institute at the University of Colorado, is the first of its kind in DSRD treatment.

As Dr. Santoro says: “We went a long way, but we have more to do!”