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

• 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
• 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

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 食物过敏（FA）在影响3200万美国人的20年中迅速增加，每年成本 250亿美元。 FA过敏症是一种潜在的威胁生命的状况，儿童增加了200-400％ 十几岁的幼儿。10花生/树坚果和芝麻过敏通常共存，持续一生，引起严重的反应， 目前无法治愈。普通治疗，预防性，即避免食物或治疗性，即 食物过敏原口服免疫疗法有限且不切实际。安全，有效和非食品限制 需要治疗。 FA主要由食物蛋白特异性免疫球蛋白E介导。 由长寿命的浆细胞（IgE+LPC）引起的是缓解FA的重要障碍。一般营养 Technology LLC（GNT）是一家纽约生物技术创业公司，正在基于FA的开创性研究 从西奈山伊甘医学院开始。我们的口服产品“ NIT-X”包含小分子 由纳米颗粒捕获的复合berberine。它显着提高了生物利用度，显示出极好的 临床前的安全性和在动物模型中的PN-IGE和防止过敏反应的降低几乎100％ 花生和树坚果过敏，与抑制IgE+浆细胞/B细胞有关，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组织化学来假设这一点。 NIT-X将是严重和多个FA的潜在新型非食品限制疗法。目标的目标 SBIR II期正在生成强大的NIT-X化学，制造和对照（CMC），沿进一步 临床前药代动力学（PK），毒理学和药理学数据，并提交IA期临床研究。我们 将执行4个具体目标：＃1生成NIT-X CMC数据，产品表征和临床前PK 轮廓; ＃2。进一步生成NIT-X临床前毒理学数据； ＃3。研究NIT-X的剂量效率 鼠模型。 ＃4。文件期IA临床试验作为正在进行的父植物IND的子程序。实心Sbir 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能够生成严格的日期 CMC，临床前PK，安全性和有效性，用于获得当前IND的主题项目的IND批准 使用NIT-X进行临床试验，用于商业化治疗FA。