Abstract Details

Title Immunosuppressive Therapies in Down Syndrome Regression Disorder: A Prospective Observational Cohort Study

Topic Child Neurology and Developmental Neurology

Presentation(s) N2 - Neuroscience in the Clinic: Neurological Care of Individuals with Down Syndrome Across the Lifespan (4:33 PM-4:45 PM)

Poster/Presentation
Number 002

Objective

This study aimed to evaluate the efficacy of immunosuppressive therapies in individuals with DSRD who were partial responders to IVIg.

Background Down Syndrome Regression Disorder (DSRD) is a neuropsychiatric condition characterized by acute or subacute cognitive and functional decline in individuals with Down syndrome. This condition occurs in the 2nd and 3rd decades of life and can be devastating for individuals and caregivers. Intravenous immunoglobulin (IVIg) has shown therapeutic benefit in most cases, however, some individuals demonstrate only partial responses.

Design/Methods In this prospective, observational, non-randomized study, individuals with DSRD who demonstrated over 50% improvement on the Bush-Francis Catatonia Rating Scale (BFCRS) or Neuropsychiatric Inventory Questionnaire (NPI-Q) following IVIg were enrolled. Participants subsequently received one of three immunosuppressive regimens: B-cell depletion (rituximab or biosimilar), Janus kinase (JAK) inhibitors, or mycophenolate mofetil (MMF). Outcomes were assessed across three timepoints: baseline, post-IVIg, and post-immunosuppression.

Results Among 126 individuals, B-cell depletion (n=63), JAK inhibition (n=34), and MMF (n=29) were administered. All treatments produced improvement on BFCRS and NPI-Q scores. B-cell depletion yielded the most benefit (BFCRS: 4.2 ± 1.1; NPI-Q: 5.1 ± 1.3), followed by JAK inhibition (BFCRS: 7.6 ± 1.4; NPI-Q: 8.8 ± 1.5), with MMF being the least effective (BFCRS: 11.3 ± 1.6; NPI-Q: 13.9 ± 1.9). ANOVA revealed significant group differences on BFCRS and NPI-Q scores (p < 0.001) between B-cell depletion and MMF and JAK inhibitors and MMF. Abnormal lumbar puncture findings predicted response to B-cell depletion (OR: 8.66, p < 0.001), and abnormal MRI predicted response to JAK inhibition (OR: 3.98, p < 0.001).

Conclusions Immunosuppressive therapy may offer additional benefit in individuals with DSRD who partially respond to IVIg. Neurodiagnostic abnormalities may guide treatment selection. These findings support the need for randomized trials evaluating precision-based immunotherapy in DSRD.

Authors/Disclosures
Jonathan Santoro, MD (Department of Neurology, Children's Hospital Los Angeles) PRESENTER	Dr. Santoro has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB. Dr. Santoro has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Cycle Pharma. Dr. Santoro has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Dianthus. Dr. Santoro has received personal compensation in the range of $500-$4,999 for serving as a Consultant for National Down Syndrome Society.
Lilia Kazerooni, BS	Miss Kazerooni has nothing to disclose.
Maeve C. Lucas, BS	Ms. Lucas has nothing to disclose.
Mariam M. Yousuf, BS	Miss Yousuf has nothing to disclose.
Samuel T. Otey, BS	Mr. Otey has nothing to disclose.
Lina Nguyen (Children's Hospital Los Angeles)	Lina Nguyen has nothing to disclose.
Nidhiben A. Anadani, MD (University Of Oklahoma Health Science Center)	Dr. Anadani has nothing to disclose.
Melanie Manning (Stanford School of Medicine)	Melanie Manning has nothing to disclose.
Angela Rachubinski, PhD	The institution of Dr. Rachubinski has received research support from NIH.
Ryan Kammeyer, MD (Childrens Hospital Colorado)	The institution of Dr. Kammeyer has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Amgen. The institution of Dr. Kammeyer has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Kammeyer has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Ogborn-Mihm Trial Lawyers. The institution of Dr. Kammeyer has received research support from Rocky Mountain Multiple Sclerosis Center.
Noemi Spinazzi, MD	Dr. Spinazzi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ionis Pharmaceuticals. Dr. Spinazzi has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Saldivar & Associates. The institution of Dr. Spinazzi has received research support from NIH.
Catherine Franklin (The University of Queensland)	Catherine Franklin has nothing to disclose.
Eileen Quinn, MD	Dr. Quinn has nothing to disclose.
Joaquin Espinosa	Joaquin Espinosa has received personal compensation in the range of $0-$499 for serving as a Consultant for Biohaven.
Michael S. Rafii, MD, PhD (USC Alzheimer'S Therapeutic Research Institute)	Dr. Rafii has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AC Immune. Dr. Rafii has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Keystone Bio. Dr. Rafii has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alzheon.

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