Low dose Naltrexone for induction of remission in inflammatory bowel disease patients

Abstract

BackgroundAround 30% of patients with inflammatory bowel disease (IBD) are refractory to current IBD drugs or relapse over time. Novel treatments are called for, and low dose Naltrexone (LDN) may provide a safe, easily accessible alternative treatment option for these patients. We investigated the potential of LDN to induce clinical response in therapy refractory IBD patients, and investigated its direct effects on epithelial barrier function.MethodsPatients not in remission and not responding to conventional therapy were offered to initiate LDN as a concomitant treatment. In total 47 IBD patients prescribed LDN were followed prospectively for 12 weeks. Where available, endoscopic remission data, serum and biopsies were collected. Further the effect of Naltrexone on wound healing (scratch assay), cytokine production and endoplasmic reticulum (ER) stress (GRP78 and CHOP western blot analysis, immunohistochemistry) were investigated in HCT116 and CACO2 intestinal epithelial cells, human IBD intestinal organoids and patient samples.ResultsLow dose Naltrexone induced clinical improvement in 74.5%, and remission in 25.5% of patients. Naltrexone improved wound healing and reduced ER stress induced by Tunicamycin, lipopolysaccharide or bacteria in epithelial barriers. Inflamed mucosa from IBD patients showed high ER stress levels, which was reduced in patients treated with LDN. Cytokine levels in neither epithelial cells nor serum from IBD patients were affected.ConclusionsNaltrexone directly improves epithelial barrier function by improving wound healing and reducing mucosal ER stress levels. Low dose Naltrexone treatment is effective and safe, and could be considered for the treatment of therapy refractory IBD patients.Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1427-5) contains supplementary material, which is available to authorized users.

Organoid Models of Colorectal Pathology: Do They Hold the Key to Personalized Medicine? A Systematic Review

“… 101 – 103 One of these studies showed that naltrexone alleviated endoplasmic reticulum stress in organoids of patients with IBD after treatment with inflammatory stimuli. 104 Interleukin-22 has shown promise as a promising target for ulcerative colitis therapy due to its role in epithelial homeostasis and repair, which lead Patnaude and colleagues 105 – 107 to trial treatment of inflammation-stimulated organoids with IL-22 that showed improved epithelial regeneration and production of membrane mucus. Han and colleagues 108 took this idea a step further and microinjected patient-derived fecal supernatants with the probiotic Lactobacillus rhamnosus .…”

Low-Dose Naltrexone (LDN)—Review of Therapeutic Utilization

“…Clinical evidence covers a broad range of sources, from initial case reports [38,39,40] to more recent randomized controlled trials [41,42]. Low-dose naltrexone could be useful for states involving chronic inflammation or immune dysregulation [43], such as Crohn’s disease [44] and fibromyalgia [41].…”

Low Dose Naltrexone - Efficacy and safety of off-label use therapy.

“…U niektórych pacjentów cierpiących na stwardnienie rozsiane i poddanych terapii LDN zaobserwowano pierwotną małopłytkowość immunologiczną (dawniej nazywaną samoistną plamicą małopłytkową (ang. idiopathic thrombocytopenic purpura, ITP), która mogła być wynikiem idiosynkrazji będącej stanem zwiększonej odczynowości organizmu na określony lek, związanej z osobniczą wrażliwością [7,39].…”