IgE Suppressing Berberine Nanomedicine for Treatment of Food Allergies

抑制 IgE 的小檗碱纳米药物治疗食物过敏

基本信息

批准号：
10698900
负责人：
Xiu-Min Li
金额：
$ 92.02万
依托单位：
GENERAL NUTRACEUTICAL TECHNOLOGY, LLC
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-05-11 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10698900
关键词：
Accidents Acute Adult Affect Age Amendment American Anaphylaxis Animal Model Annual Reports Antibodies Area Under Curve B-Lymphocytes Berberine Biochemistry Biological Availability Biotechnology Body Surface Botanicals Categories Chemistry Child Chronic Clinical Clinical Research Clinical Trials Data Dose Double-Blind Method Drug Kinetics Encapsulated Epithelial Cells FDA approved Food Food Hypersensitivity Generations Goals Heavy Metals Hematology Histamine Histology Hypersensitivity IgE Immunity Immunoglobulin A Immunoglobulin G Immunosuppression Individual Industry Inflammation Interferon Type II Interleukin-10 Interleukin-4 Investigational Drugs Laboratories Life Marketing Mediating Morbidity - disease rate Mus Nut Hypersensitivity Nutraceutical Nuts Oral Outcome Parents Persons Pesticides Pharmaceutical Preparations Pharmacology Pharmacology and Toxicology Phase Phase Ia Clinical Trial Placebo Control Placebos Plasma Plasma Cells Preparation Production Proteins Reaction Research Residual state Risk Safety Sesame - dietary Small Business Innovation Research Grant Solid Technology Teenagers Testing Therapeutic Time Toddler Toxicology Trees Work absorption anti-IgE commercialization common treatment cost drug development food allergen food avoidance high risk immunoreaction innovation intestinal epithelium manufacture mast cell medical schools meetings microbial mortality mouse model nano nanomedicine nanoparticle novel novel therapeutics omalizumab oral immunotherapy phase 1 designs phase 2 designs phase 2 study phase I trial pre-clinical preclinical safety programs prophylactic protective effect small molecule transcriptomics

项目摘要

ABSTRACT Food allergy (FA) has rapidly increased over 2 decades affecting 32 million Americans, with annual costs of $25 billion. FA anaphylaxis, a potentially life-threatening condition, increased 200-400% in children from toddlers to teens.10 Peanut/ tree nut and sesame allergy often co-exist, last a lifetime, cause severe reactions, and there is currently no cure. Common treatments, either prophylactic i.e., food avoidance, or therapeutic i.e., food allergen oral immunotherapy are limited and impractical. Safe, effective, and non-food restricted therapeutics are needed. FA is primarily mediated by food protein specific immunoglobulin E. Persistent IgE caused by long-lived plasma cells (IgE+LPC) is a significant barrier to FA mitigation. General Nutraceutical Technology LLC (GNT), a NY-based biotechnology startup, is building on groundbreaking research for FA started at Icahn School of Medicine at Mount Sinai. Our oral product “NIT-X” contains the small molecule compound berberine captured by nanoparticles. It significantly increased bioavailability, showed excellent preclinical safety and nearly 100% reduction of PN-IgE and protection against anaphylaxis in animal model of peanut and tree nut allergies, associated with suppressing IgE+ plasma cells/B cells, reducing IL-4, increasing IFN-γ, inducing a distinct B cell transcriptomic profile. We hypothesize that by restoring balanced immunity. NIT-X will be a potentially novel non-food restricted therapeutic for severe and multiple FAs. The goals of this SBIR Phase II are generating robust NIT-X Chemistry, Manufacturing and Control (CMC), along further preclinical pharmacokinetic (PK), toxicology and pharmacology data, and file the phase Ia clinical study. We will conduct 4 Specific Aims: #1 Generating NIT-X CMC data, characterization of product and preclinical PK profile; #2. Further generation of data on NIT-X preclinical toxicology; #3. Investigate dose efficacy of NIT-X in murine models. #4. File phase Ia clinical trial as a sub-program to an ongoing parent botanical IND. Solid SBIR phase I feasibility data and strong team and design for phase II study enable GNT to generate rigorous date for CMC, preclinical PK, safety, and efficacy for obtaining approval of IND for a subproject to the current IND for clinical trials with NIT-X, towards commercialization for treating FA.

抽象的 20 年来，食物过敏 (FA) 迅速增加，影响了 3200 万美国人，每年造成损失 250 亿美元的 FA 过敏反应（一种可能危及生命的疾病）在儿童中增加了 200-400%。幼儿到青少年。10 花生/木本坚果和芝麻过敏通常共存，持续一生，引起严重反应，目前还没有常见的治疗方法，无论是预防性的，即避免食物，还是治疗性的，即，食物过敏原口服免疫疗法是有限且不切实际的，安全、有效且不受食物限制。 FA 主要由食物蛋白特异性免疫球蛋白 E 介导。持续性 IgE。由长寿命浆细胞 (IgE+LPC) 引起的 FA 缓解是一个重要障碍。 Technology LLC (GNT) 是一家总部位于纽约的生物技术初创公司，正在以 FA 的突破性研究为基础我们的口腔产品“NIT-X”含有小分子。纳米颗粒捕获的复合小檗碱显着提高了生物利用度，表现出优异的性能。临床前安全性，PN-IgE 减少近 100%，并在动物模型中预防过敏反应花生和坚果过敏，与抑制 IgE+ 浆细胞/B 细胞、减少 IL-4、增加 IFN-γ，诱导独特的 B 细胞转录组谱，我们通过恢复平衡的免疫来捕获这一点。 NIT-X 将成为一种潜在的新型非食物限制疗法，用于治疗严重和多种 FA。 SBIR 第二阶段正在生成强大的 NIT-X 化学、制造和控制 (CMC)，并进一步临床前药代动力学（PK）、毒理学和药理学数据，并归档Ia期临床研究。将实现 4 个具体目标：#1 生成 NIT-X CMC 数据、产品表征和临床前 PK 概况；#2. 进一步生成 NIT-X 临床前毒理学数据；#3。 #4. 将 Ia 期临床试验作为正在进行的母体固体 SBIR 的子计划进行归档。第一阶段的可行性数据以及第二阶段研究的强大团队和设计使 GNT 能够生成严格的数据子项目获得 IND 批准的 CMC、临床前 PK、安全性和有效性 NIT-X 的临床试验，旨在实现治疗 FA 的商业化。