Dataset Information

Engineered Polymersomes for the Treatment of Fish Odor Syndrome: A First Randomized Double Blind Olfactory Study.

ABSTRACT: Trimethylamine (TMA) is a metabolite overtly present in patients suffering from trimethylaminuria (TMAU), a rare genetic disorder characterized by a strong "fishy" body odor. To date, no approved pharmacological treatment to sequester excess TMA on the skin of patients exists. Here, transmembrane pH gradient poly(isoprene)-block-poly(ethylene glycol) (PI-b-PEG) polymersomes are investigated for the topical removal of TMA. PI-b-PEG amphiphiles of varying chain length are synthesized and evaluated for their ability to form vesicular structures in aqueous media. The optimization of the PI/PEG ratio of transmembrane pH gradient polymersomes allows for the rapid and efficient capture of TMA both in solution and after incorporation into a topical hydrogel matrix at the pH of the skin. A subsequent double blind olfactory study reveals a significant decrease in perceived odor intensity after application of the polymersome-based formulation on artificial skin substrates that has been incubated in TMA-containing medium. This simple and novel approach has the potential to ease the burden of people suffering from TMAU.

SUBMITTER: Schmidt AC

PROVIDER: S-EPMC7175261 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Engineered Polymersomes for the Treatment of Fish Odor Syndrome: A First Randomized Double Blind Olfactory Study.

Schmidt Aaron C AC Hebels Erik R ER Weitzel Charlotte C Kletzmayr Anna A Bao Yinyin Y Steuer Christian C Leroux Jean-Christophe JC

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20200309 8

Trimethylamine (TMA) is a metabolite overtly present in patients suffering from trimethylaminuria (TMAU), a rare genetic disorder characterized by a strong "fishy" body odor. To date, no approved pharmacological treatment to sequester excess TMA on the skin of patients exists. Here, transmembrane pH gradient poly(isoprene)-block-poly(ethylene glycol) (PI-b-PEG) polymersomes are investigated for the topical removal of TMA. PI-b-PEG amphiphiles of varying chain length are synt ...[more]

PMID: 32328434

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Project description:ObjectivesThe aim of this study was to determine whether behavioral responses elicited by olfactory stimulation are a predictor of conscious behavioral response and prognosis of patients with disorders of consciousness (DOC).MethodsTwenty-three DOC patients (8 unresponsive wakefulness syndrome [UWS]; 15 minimally conscious state [MCS]) were recruited for this study in which 1-Octen-3-ol (familiar neutral odor) and pyridine were used to test odor behavioral responses, and water was used as an odorless stimulus. One rater presented the three odors in front of each patient's nose randomly, and another one videotaped all behavioral responses (e.g., pouting, wrinkling nose, slightly shaking head, frowning, etc.). Two independent raters, blind to the stimuli and the patient's diagnosis, gave the behavioral results according to the recorded videos. One-, 3-, and 6-month follow-up evaluations were conducted to obtain a good prognostic value.ResultsAll MCS patients showed behavioral responses to the 1-Octen-3-ol stimulus; nine MCS and one UWS showed olfactory emotional responses to the pyridine, and two MCS showed olfactory emotional responses to the water stimulus. The incidence of behavioral response was significantly higher using 1-Octen-3-ol than it was for water by McNemar test (p < 0.001), significantly higher using pyridine than it was for water (p < 0.01). The χ2 test results indicated that there were significant differences between MCS and UWS to 1-Octen-3-ol (p < 0.001). For MCS patients, the incidence of behavioral response was no different between using 1-Octen-3-ol and pyridine (p > 0.05). There was no significant relationship between the olfactory behavioral response and the improvement of consciousness based on the χ2 test analysis (p > 0.05).ConclusionOlfactory stimuli, especially for the familiar neutral odor, might be effective for eliciting a conscious behavioral response and estimating the clinical diagnosis of DOC patients.Clinical trial registration[https://clinicaltrials.gov/ct2/show/NCT03732092], [identifier NCT03732092].

Project description:BackgroundImpaired wound healing is a growing medical problem and very few approved drugs with documented clinical efficacy are available. CXCL12-expressing lactic acid bacteria, Limosilactobacillus reuteri (ILP100-Topical), has been demonstrated to accelerate wound healing in controlled preclinical models. In this first-in-human study, the primary objective was to determine safety and tolerability of the drug candidate ILP100-Topical, while secondary objectives included assessments of clinical and biologic effects on wound healing by traditionally accepted methods and explorative and traceable assessments.MethodsSITU-SAFE is an adaptive, randomised, double-blind, placebo-controlled, first-in-human phase 1 trial (EudraCT 2019-000680-24) consisting of a single (SAD) and a multiple ascending dose (MAD) part of three dose cohorts each. The study was performed at the Phase 1 Unit, Uppsala University Hospital, Uppsala, Sweden. Data in this article were collected between Sep 20th, 2019 and Oct 20th 2021. In total 240 wounds were induced on the upper arms in 36 healthy volunteers. SAD: 12 participants, 4 wounds (2/arm), MAD: 24 participants, 8 wounds (4/arm). Wounds in each participant were randomised to treatment with placebo/saline or ILP100-Topical.FindingsIn all individuals and doses, ILP100-Topical was safe and well-tolerated with no systemic exposure. A combined cohort analysis showed a significantly larger proportion of healed wounds (p = 0.020) on Day 32 by multi-dosing of ILP100-Topical when compared to saline/placebo (76% (73/96) and 59% (57/96) healed wounds, respectively). In addition, time to first registered healing was shortened by 6 days on average, and by 10 days at highest dose. ILP100-Topical increased the density of CXCL12+ cells in the wounds and local wound blood perfusion.InterpretationThe favourable safety profile and observed effects on wound healing support continued clinical development of ILP100-Topical for the treatment of complicated wounds in patients.FundingIlya Pharma AB (Sponsor), H2020 SME Instrument Phase II (#804438), Knut and Alice Wallenberg foundation.

Dataset Information

Engineered Polymersomes for the Treatment of Fish Odor Syndrome: A First Randomized Double Blind Olfactory Study.

Publications

Engineered Polymersomes for the Treatment of Fish Odor Syndrome: A First Randomized Double Blind Olfactory Study.

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