Acute Corticotropin-Releasing Factor Receptor Type 2 Agonism Results in Sustained Symptom Improvement in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

• DOI: 10.3389/fnsys.2021.698240
• Publication Date: 2021-09-04T01:46:19Z
• Authors: Gerard Pereira; Hunter Gillies; Sanjay Chanda; Michael Corbett; Suzanne D. Vernon; Tina Milani; Lucinda Bateman
• Keywords: Tolerability; Encephalomyelitis

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex multi-symptom disease with widespread evidence of disrupted systems. The authors hypothesize that it caused by the upregulation corticotropin-releasing factor receptor type 2 (CRFR2) in raphé nuclei and limbic system, which impairs ability to maintain homeostasis. propose utilizing agonist-mediated endocytosis downregulate CRFR2.This open-label trial tested safety, tolerability efficacy an acute dose CT38s (a short-lived, CRFR2-selective agonist, no known off-target activity) 14 ME/CFS patients. was subcutaneously-infused at one four dose-levels (i.e., infusion rates 0.01, 0.03, 0.06, 0.20 μg/kg/h), for maximum 10.5 h. Effect measured as pre-/post-treatment change mean 28-day total daily symptom score (TDSS), aggregated 13 individual patient-reported symptoms.ME/CFS patients were significantly more sensitive transient hemodynamic effects CRFR2 stimulation than healthy subjects prior trial, supporting hypothesized upregulation. Adverse events generally mild, resolved without intervention, difficult distinguish from symptoms, role disease. associated improvement TDSS sustained (over least 28 days post-treatment) correlated both exposure pre-treatment severity. At rate 0.03 μg/kg/h, improved -7.5 ± 1.9 (or -25.7%, p = 0.009), all monitored symptoms improving.The supports hypothesis upregulated ME/CFS, agonism may be viable treatment approach warranting further study.ClinicalTrials.gov, identifier NCT03613129.