Therapies for Down Syndrome Regression Disorder

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.

Inclusion Criteria: * Individuals with DS between the ages of 8 and 30 years, inclusive. DS is broadly defined to include complete trisomy 21, Robertsonian translocation trisomy 21, partial trisomy 21 (segmental duplication), and mosaic trisomy 21. * Diagnosis of possible or probable DSRD per 2022 consensus guidelines. * Must agree to random treatment assignment. * Must agree to complete a washout of any medications intended to treat symptoms of DSRD or that may interfere with study interventions. * Must be able to present with a study partner or legal guardian at all study visits. Exclusion Criteria: General * Weight less than 40 kg. * Pregnant or breast feeding. * Past or current tobacco smoking. * Poor venous access not allowing repeated blood tests or non-compliance with venipuncture requirements. * Known allergies, hypersensitivity, or intolerance to lorazepam, IVIG, or tofacitinib. * Participants may be excluded for other unforeseen reasons or confounding reasons for DSRD symptoms at the study doctor's discretion. Co-occurring Conditions * Any co-occurring genetic disorder. * Active symptomatic cardiac disease. * Clinically significant chronic or active viral infection, including but not limited to HIV, hepatitis, CMV, EBV, HSV or untreated tuberculosis. * Untreated chronic or active bacterial infection. * Untreated hypothyroidism or hyperthyroidism. * History of disseminated herpes zoster, disseminated herpes simplex, or recurrent localized dermatomal herpes zoster. * History of malignancy (solid tumor or leukemia). * Moyamoya syndrome or stroke (active or prior). * Baseline abnormal renal function indicative of moderate or severe renal disease by eGFR \