Linking the IL-17A immune response with NMR-based faecal metabolic profile in IBD patients treated with Mastiha.

Dysregulation of intestinal immune response plays a critical role in the pathogenesis of Inflammatory Bowel Disease (IBD). Mastiha's anti-inflammatory properties are well established. Our aim was to investigate Mastiha's regulatory effect on IL-17A serum levels in IBD patients. Alterations of the faecal metabolome as a functional readout of microbial activity were explored. A randomized, double-blind, placebo-controlled, parallel-group design was applied for a total of 3 months in active and 6 months in inactive IBD patients. Serum IL-17A increased significantly in Mastiha group (p = 0.006), and the mean change differed significantly between Mastiha and placebo (p = 0.003) even after adjusting for age, sex and BMI (p = 0.001) in inactive patients. In inactive UC patients IL-17A decreased significantly only in placebo (p = 0.033). No significant differences were detected in active disease. Faecal metabolomics indicated that intervention with Mastiha influenced considerably the metabolic profile of IBD patients in remission exhibiting, in between others, increased levels of glycine and tryptophan. Glycine has been proposed to have a therapeutic effect against IBD, while tryptophan derivatives are involved in immunoregalutory mechanisms, such as the Th17 cells differentiation. Thus, it is quite possible that the immunoregulatory role of Mastiha in quiescent IBD involves the regulation of Th17 cells function and differentiation.

Contact Dermatitis From Gum Mastic (Pistacia lentiscus) and Gum Storax (Liquidambar styraciflua) in Mastisol-Allergic Patients.

BACKGROUND: Mastisol Liquid Adhesive is widely used on the skin, especially after surgical procedures. It contains gum mastic, gum storax, methyl salicylate, and ethanol. OBJECTIVE: The aims of the study were to review our experience patch testing patients allergic to Mastisol and to assess coreacting substances. METHODS: We identified 18 patients who were allergic to Mastisol. Most of these had a history of postoperative or cardiac electrode dermatitis and underwent patch testing with multiple surgically related substances, including ingredients of Mastisol, compound tincture of benzoin, and fragrance-related ingredients and botanicals. RESULTS AND CONCLUSIONS: Among Mastisol-allergic patients, 13 (72%) of 18 were allergic to gum mastic, whereas 7 (44%) of 16 were allergic to gum storax. There was frequent coreactivity with various fragrance-related materials, including Majantol, Styrax benzoin, Myroxylon balsamum, Myroxylon pereirae, propolis, and others. Two gum mastic-allergic patients had positive patch tests with hydroperoxides of linalool and several other linalool-containing essential oils. As gum mastic contains linalool, it may explain some gum mastic reactions. Among patients without a history of postoperative contact dermatitis, 1 (0.4%) of 250 was patch test positive for gum mastic. This patient had allergic contact dermatitis from fragrances, so the gum mastic reaction was likely a true-positive relevant reaction.

A First-in-Human Phase 1 Randomized Single and Multiple Ascending Dose Study of RPh201 in Healthy Volunteers.

RPh201 is a drug extracted from gum mastic that has been studied for its anti-inflammatory and antibacterial properties. Preclinical studies of RPh201 demonstrated neuroprotective and neuroenhancing effects. Toxicology studies in animals did not reveal safety concerns or genotoxic effects. This single-center, phase 1, randomized, placebo-controlled, double-masked study in healthy volunteers assessed the safety and tolerability of RPh201, and determined the highest tolerated dose. There were 2 parts: a single ascending dose (SAD) stage, followed by a multiple ascending dose (MAD) stage. Three dosing arms were included in each stage (5 mg, 10 mg, and 20 mg). Safety data in the lower dosing arms were evaluated before higher doses were initiated. Eighteen participants were randomized in the SAD stage: 12 to RPh201 (4 at each dose) and 4 to placebo. Twenty-one participants were randomized in the MAD stage, of which 13 received RPh201. All 18 participants in the SAD stage completed treatment. Sixteen of the 21 participants in the MAD stage completed treatment. The most frequently reported adverse events were local injection site pain and erythema. No deaths or adverse events related to changes in vital signs or electrocardiograms were reported. No occurrences of suicidal behavior or ideation were reported.

Randomized Controlled Phase 2a Study of RPh201 in Previous Nonarteritic Anterior Ischemic Optic Neuropathy.

BACKGROUND: No proven treatment exists for nonarteritic anterior ischemic optic neuropathy (NAION), either in the acute or late phase. OBJECTIVE: To assess safety and changes in visual function and structure after RPh201/placebo treatment in participants with previous NAION. DESIGN AND SETTING: Phase 2a, single-site, prospective, randomized, placebo-controlled, double-masked trial (registration NCT02045212). MAIN OUTCOMES MEASURES: Early Treatment Diabetic Retinopathy Study best-corrected visual acuity (BCVA), visual fields, retinal nerve fiber layer, and visual evoked potential at weeks 13, 26, and after a 13-week wash-out ("off-drug") period; and safety. STUDY POPULATION: Twenty-two participants aged 18 years or older with previous NAION. INTERVENTION(S): RPh201 (20 mg) or placebo (cottonseed oil vehicle) administered subcutaneously twice weekly at the study site. RESULTS: Thirteen men and 9 women were randomized, of which 20 completed all visits. The mean (±SD) age was 61.0 ± 7.6 years. In a post hoc analysis, after 26 weeks of treatment, BCVA improved by ≥15 letters in 4/11 (36.4%) eyes with RPh201, compared to 1/8 (12.5%) eyes with placebo (P = 0.24). Overall, 7/11 (63.6%) of participants on RPh201 showed some improvement in BCVA, compared with 3/8 (37.5%) on placebo (P = 0.26). Improvement in BCVA from a calculated baseline was 14.8 ± 15.8 letters for RPh201 and 6.6 ± 15.3 for placebo (P = 0.27). Of the 154 adverse effects (AEs), 52 were considered related to the study procedures/treatment. Across the study and 1,017 injections, the most frequently reported AE was injection site pain (23 events in 5 participants). There were no clinically significant changes in vital signs or laboratory values. CONCLUSIONS: This Phase 2a was designed to assess safety, feasibility, and explore potential efficacy signals in treating previous NAION with RPh201. No safety concerns were raised. The results support a larger trial in patients with previous NAION.