Enlarging spectrum of Triple Positives on GENIE: A cohort review and a case study supporting a novel approach to treatment of complex CIRS using a prodrome biomarker

Abstract

In 2024 we published the transcriptomic basis for a unique fingerprint for Parkinson’s disease (PD-CIRS) using GENIE, a gene activation assay. Called Triple Positives (T3+), this fingerprint was expanded in 2025 to include the causative role of exposure to bacterial endotoxins in patients with T3+ and specific abnormalities found on NeuroQuant (NQ), a volumetric assay measuring eleven brain areas. We are now finding T3+ in asymptomatic patients who develop brain injury subsequent to exposure to water-damaged buildings with such exposure being marked by the emergence of three new biomarkers, AKT, RELA and TLR2. Patients with these markers present an objective indicator of CNS injury similar to concept to subjective findings found in prodromic indicators of active Parkinson’s disease when CIRS is present. Learning how to recognize and use T3+ provides insight into the basis for an expanded approach to diagnosis and treatment of Chronic Inflammatory Response Syndrome (CIRS). We now recognize that the CIRS cases that are the most refractory to treatment are T3+ with elevated levels of dispersion. We present here a refractory T3+ case with excellent therapeutic benefit seen following use of higher doses of vasoactive intestinal polypeptide (VIP). We report a new roster of 266 cases of T3+, a larger control group of 55 patients, and before and after treatment group of 25 cases that support the use of T3+ in clinical practice.