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Phosphorylation of the ER stress sensor IRE1a following stimulation of astrocytes with pro-inflammatory cytokines such as IL-1β and TNF results in full translation of the transcription factor XBP1, which has been shown to drive a subset of astrocytes towards pathogenicity in MS 138–140

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Alternative TB-500 protocols for different goals Daily low-dose protocol For patients who prefer more frequent, lower-volume injections: Dose: 750 mcg – 1 mg daily , subcutaneous Duration: 12 weeks continuous, then 4 weeks off Provides steady-state tissue levels without peaks and troughs of twice-weekly dosing Preferred by some patients with needle anxiety (smaller volume per injection) Body-weight-based TB-500 dosing Some practitioners calculate by weight for greater precision: Loading: 30–60 mcg/kg per injection , twice weekly Maintenance: 30 mcg/kg once weekly For a 75 kg patient: loading = 2.25–4.5 mg per injection