A Phase 1/2 Study of Flavocoxid, an Oral NF-κB Inhibitor, in Duchenne Muscular Dystrophy

• Published in: Brain sciences Vol. 11; no. 1; p. 115
• Main Authors: Vita, Gian Luca, Sframeli, Maria, Licata, Norma, Bitto, Alessandra, Romeo, Sara, Frisone, Francesca, Ciranni, Annamaria, Pallio, Giovanni, Mannino, Federica, Aguennouz, M'Hammed, Rodolico, Carmelo, Squadrito, Francesco, Toscano, Antonio, Messina, Sonia, Vita, Giuseppe
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 16.01.2021; MDPI
• Subjects: anti-inflammatory agent; Anti-inflammatory agents; antioxidant; Antioxidants; Arachidonate 5-lipoxygenase; Baicalin; Biological activity; Body weight; Catechin; Duchenne muscular dystrophy; Duchenne's muscular dystrophy; FDA approval; flavocoxid; Flavonoids; Glutathione peroxidase; Hydrogen peroxide; Inflammation; Informed consent; Interleukin 1; Kinases; Laboratories; Lipoxygenase; Muscular dystrophy; Mutation; NF-κB inhibitor; NF-κB protein; Patients; phase 1/2 study; Placebos; Prostaglandin endoperoxide synthase; Proteins; Statistical analysis; Steroid hormones; Steroids; Tumor necrosis factor; Tumor necrosis factor-TNF; United States > US; Italy; antioxidant; phase 1/2 study; NF-κB inhibitor; Duchenne muscular dystrophy; flavocoxid; anti-inflammatory agent
• ISSN: 2076-3425; 2076-3425
• DOI: 10.3390/brainsci11010115

Flavocoxid is a blended extract containing baicalin and catechin with potent antioxidant and anti-inflammatory properties due to the inhibition of the cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) enzymes, nuclear factor-κB (NF-κB), tumor necrosis factor (TNF)-alpha, and the mitogen-activated protein kinases (MAPKs) pathways. This phase 1/2 study was designed to assess the safety and tolerability of flavocoxid in patients with Duchenne muscular dystrophy (DMD). Thirty-four patients were recruited: 17 were treated with flavocoxid at an oral dose of 250 or 500 mg, according to body weight, for one year; 17 did not receive flavocoxid and served as controls. The treatment was well tolerated and nobody dropped out. Flavocoxid induced a significant reduction in serum interleukin (IL)-1 beta and TNF-alpha only in the group of DMD boys on add-on therapy (flavocoxid added to steroids for at least six months). The decrease in IL-1 beta was higher in younger boys. The serum H O concentrations significantly decreased in patients treated with flavocoxid alone with a secondary reduction of serum glutathione peroxidase (GPx) levels, especially in younger boys. The exploratory outcome measures failed to show significant effects but there was a trend showing that the younger boys who received treatment were faster at performing the Gowers' maneuver, while the older boys who received treatment were faster at doing the 10-m walk test (10MWT). Therefore, a double-blind, placebo-controlled study for at least two/three years is warranted to verify flavocoxid as a steroid substitute or as add-on therapy to steroids.