A Phase 1/2 Study of Flavocoxid, an Oral NF-κB Inhibitor, in Duchenne Muscular Dystrophy.
Gian Luca VitaMaria SframeliNorma LicataAlessandra BittoSara RomeoFrancesca FrisoneAnnamaria CiranniGiovanni PallioFederica ManninoM'Hammed AguennouzCarmelo RodolicoFrancesco SquadritoAntonio ToscanoSonia MessinaGian Luca VitaPublished in: Brain sciences (2021)
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 H2O2 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.
Keyphrases
- duchenne muscular dystrophy
- nuclear factor
- anti inflammatory
- oxidative stress
- rheumatoid arthritis
- body weight
- signaling pathway
- end stage renal disease
- open label
- muscular dystrophy
- physical activity
- toll like receptor
- chronic kidney disease
- peritoneal dialysis
- clinical trial
- mesenchymal stem cells
- pi k akt
- diabetic rats
- community dwelling
- immune response
- smoking cessation
- stress induced
- low density lipoprotein