Recent published case reports and clinical experience of the investigators indicate Down Syndrome Regression Disorder (DSRD) may be successfully treated with immune-modulating therapies, in addition to current pharmacologic options. This study is a multidimensional clinical trial designed to advance the understanding of the etiology of DSRD and to evaluate the safety and efficacy of three distinct therapeutic approaches to treating DSRD: (1) the benzodiazepine lorazepam (Ativan™) (2) intravenous immunoglobulin (IVIG, Gammagard™) or (3) the JAK inhibitor tofacitinib (Xeljanz™). Participants will be randomized into one of the three treatment arms above for the 12-week study period, with a subset of participants undergoing an initial 12-week observational period.~Specific Aims:~To define the relative safety profile of lorazepam, IVIG, and tofacitinib in DSRD.~To compare the efficacy of lorazepam, IVIG, and tofacitinib in DSRD.~To investigate potential mechanisms underlying DSRD and its response to therapies.
Individuals with Down syndrome (DS) have an increased risk of numerous co-occurring conditions, including the neuropsychiatric condition known as Down Syndrome Regression Disorder (DSRD). A DSRD diagnosis often includes a sub-acute onset of catatonia, mutism, depersonalization, loss of ability to perform activities of daily living, hallucinations, delusions, and aggression and is most commonly observed in adolescents and young adults.~The study evaluates the safety and efficacy of three currently prescribed therapies: lorazepam, intravenous immunoglobulin (IVIG) and tofacitinib.