5-Aminolevulinic Acid as a Novel Therapeutic for Inflammatory Bowel Disease.

Vipul Yadav,Yang Mai,Laura E Mccoubrey,Satofumi Kawata,Yasufumi Wada,Abdul W Basit,Motoyasu Tomioka,Shrikant Charde

doi:10.3390/biomedicines9050578

Vipul Yadav, Yang Mai + Show 6 more

Open Access

https://doi.org/10.3390/biomedicines9050578

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Journal: Biomedicines	Publication Date: May 20, 2021
Citations: 10	License type: CC BY 4.0

Affiliation: University College London, Oncolys BioPharma (Japan)

Abstract

5-Aminolevulinic acid (5-ALA) is a naturally occurring nonprotein amino acid licensed as an optical imaging agent for the treatment of gliomas. In recent years, 5-ALA has been shown to possess anti-inflammatory and immunoregulatory properties through upregulation of heme oxygenase-1 via enhancement of porphyrin, indicating that it may be beneficial for the treatment of inflammatory conditions. This study systematically examines 5-ALA for use in inflammatory bowel disease (IBD). Firstly, the ex vivo colonic stability and permeability of 5-ALA was assessed using human and mouse fluid and tissue. Secondly, the in vivo efficacy of 5-ALA, in the presence of sodium ferrous citrate, was investigated via the oral and intracolonic route in an acute DSS colitis mouse model of IBD. Results showed that 5-ALA was stable in mouse and human colon fluid, as well as in colon tissue. 5-ALA showed more tissue restricted pharmacokinetics when exposed to human colonic tissue. In vivo dosing demonstrated significantly improved colonic inflammation, increased local heme oxygenase-1 levels, and decreased concentrations of proinflammatory cytokines TNF-α, IL-6, and IL-1β in both plasma and colonic tissue. These effects were superior to that measured concurrently with established anti-inflammatory treatments, ciclosporin and 5-aminosalicylic acid (mesalazine). As such, 5-ALA represents a promising addition to the IBD armamentarium, with potential for targeted colonic delivery.

Highlights

Introduction published maps and institutional affilThe global prevalence of inflammatory bowel disease (IBD) has risen significantly in the last 30 years, with an increase of 85.1% in global cases from 1990 to 2017 [1,2]
5-Aminolevulinic acid (5-ALA) was found to be completely stable in both mouse and human faecal slurry with no drug degradation observed over 24 h (Figure 3A)
As the total intestinal transit time of the general human population is around 27 h, it can be assumed that 5-ALA will not be microbially degraded in the GI tract [55]

Summary

Introduction

The global prevalence of inflammatory bowel disease (IBD) has risen significantly in the last 30 years, with an increase of 85.1% in global cases from 1990 to 2017 [1,2]. IBD carries a heavy burden for both patients and healthcare providers [3]. In the U.S, lifetime healthcare costs for individuals with IBD average at over half a million dollars [4]. Patients suffer from noninfectious chronic inflammation of the gastrointestinal (GI) tract, resulting in common symptoms of abdominal pain, diarrhoea, weight loss, rectal bleeding, and malnutrition [5,6]. It is recognised that these symptoms significantly impact patients’. In CD, inflammation can occur at any point along the GI tract and is typically transmural, affecting all layers of intestinal tissue [9,10]. GI inflammation in UC is confined to the iations

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