Abstract
Background. Hyaluronan (HA) is a naturally occurring glycosaminoglycan polymer produced in all vertebrates, and usually present at the high molecular weight (>106 Da). Low molecular weight HA has signaling properties, and fragments ~35 kDa size (HA35) have biological activity in eliciting epithelial β-defensins and tight junction proteins, notably ZO1, important components of innate host defense arsenal of the gut barrier in preclinical models. Safety, tolerability, impact on metabolism, gut permeability, and microbiome composition in healthy human subjects were all evaluated prospectively. Methods. Pharmaceutical grade HA35 (140 mg in water once daily for seven days), was administered orally to 20 healthy subjects (30.7 ± 5.6 years). Demographical, clinical, biochemical laboratory tests, metabolic function and stool microbiome composition were measured on Day 0, 8 and 28. Results. HA35 was tolerated well in all subjects with no serious adverse events in any subjects. No statistical differences in any of the measurements were seen among the study group over the course of the trial. In aggregate there were no changes in demographical, clinical, biochemical laboratory tests, and metabolic function or microbiome composition during the 28-day study. Conclusion. Oral HA35 administration (140 mg/day) is a safe treatment in healthy individuals and does not affect metabolic, inflammatory or microbiome parameters.
Highlights
Hyaluronan (HA) is a linear glycosaminoglycan polymer consisting of repeating disaccharides of β-glucuronic acid and N-acetylglucosamine [1]
Non-hospitalized, human subjects of both genders were screened for inclusion in a prospective study of oral HA35 once daily for seven days after which they were followed for a total of 28 days
To the best of our knowledge, this Food and Drug Administration approved longitudinal trial is the first study of oral HA35 administered to healthy human subjects for determining its safety and tolerability
Summary
Hyaluronan (HA) is a linear glycosaminoglycan polymer consisting of repeating disaccharides of β-glucuronic acid and N-acetylglucosamine [1]. Recent studies have shown that exogenous, specific-sized HA of an average molecular weight of 35 Kda (HA35), but not smaller or larger polymers, dampens inflammatory responses in murine models of inflammation, including bacterial-driven colitis and alcohol-mediated injury [14,15,16,17]. These beneficial effects are mediated by HA35 interaction with multiple HA receptors, including. These studies are of high clinical relevance, due to the availability of pharmaceutical grade HA35 that has the potential human use in targeting tissue inflammation
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