BioFe Mechanism of Action for the treatment of iron deficiency anemia

BioFe 治疗缺铁性贫血的作用机制

• 批准号: 10009565
• 负责人: Darren Wolfe
• 金额: $ 30万
• 依托单位: SIDERO BIOSCIENCE, LLC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10009565
• 关键词: Address; Anemia; Anemia due to Chronic Disorder; Animal Model; Apical; Binding; Biological; Biological Availability; Biological Sciences; Biology; Blood; Blood Circulation; Caco-2 Cells; Carrier Proteins; Cells; Characteristics; Child; Chronic; Clinical; Clinical Data; Clinical Trials; Complex; Consumption; Data; Dietary Iron; Disease; Distress; Dried Yeast; Elderly; Electron Microscopy; Enterocytes; FTH1 gene; Female of child bearing age; Ferritin; Ferrous Sulfate; Funding; H ferritin; Health; Human; Human Milk; Immunoglobulin Domain; Individual; Infant; Infection; Inflammation; Inflammatory; Inflammatory Response; International; Intestines; Intravenous; Iron; Iron deficiency anemia; Knowledge; L-ferritin; Laboratories; Letters; Malnutrition; Marketing; Meat; Mediating; Mediation; Membrane; Methods; Nursing infant; Nutrition Disorders; Oral; Outcome Study; Pathway interactions; Performance; Phase; Placebos; Plant Roots; Plants; Positioning Attribute; Probiotics; Process; Protein Export Pathway; Proteins; Regulation; Reporting; Risk; Rodent; Salts; Serum; Site; Small Business Innovation Research Grant; Small Business Technology Transfer Research; Source; Stomach; Surface; T-Lymphocyte; Technology; Testing; Therapeutic; Time; Tissues; Toxic effect; Woman; Yeasts; absorption; age group; apical membrane; base; basolateral membrane; divalent metal; evidence base; gastrointestinal; gut microbiome; gut microbiota; hepcidin; indexing; interest; intestinal epithelium; iron absorption; iron deficiency; iron supplement; medical food; metal transporting protein 1; nanoparticle; nonhuman primate; novel; oral supplementation; pathogen; pre-clinical; prevent; receptor; response; side effect; standard of care; success; treatment comparison; uptake

Iron deficiency (ID) is the most common and widespread nutritional disorder worldwide with over 2 billion people suffering significant negative health effects. There is a widespread, serious misperception that oral iron supplements are safe and effective at alleviating ID; yet in a recent Cochrane review of 67 clinical trials, women taking oral iron supplements had just a 38% decreased risk of ID at the end of treatment compared to placebo. Moreover, these subjects had a 114% increased risk of side effects, the vast majority of which were associated with gastrointestinal (GI) disturbance. The current standard of care for treating ID involves iron salts or more recently iron nanoparticles which are degraded in the stomach and release elemental iron. SideroBiosciences has developed a disruptive technology consisting of nutritional yeast modified to express a H-ferritin:iron complex known as BioFe. The concept of using an H- ferritin;iron complex is rooted in mimicking iron delivery from breast milk and using nutritional yeast provides an easily accessible and economical platform for marketing and consumption by many different cultures and age groups. That the ferritin:iron complex in BioFe is specifically H- ferritin distinguishes it from L-ferritin or plant ferritin, both of which have had limited success as iron supplements because they are degraded in the gut to release the iron and thus use the same pathway into enterocytes as iron salts and thus their performance is at best similar to the iron salts. BioFe has been successfully tested in rodents, non-human primates and humans (including a STTR funded study). While the absorption and secretion of elemental iron across the membranes of intestinal enterocytes are relatively well described, the receptor(s), transporter(s), and regulatory mechanism(s) for H-Ferritin:Iron complexes have not been described. In multiple discussions with potential marketing partners, SideroBiosciences has been consistently queried for more details on how the entry of the ferritin;iron complex into the body are different from iron salts. Therefore,to address these questions, we have provided exciting pilot data to pursue in this application that will interrogate mechanisms by which Ferritin:Iron complexes are transported across the apical membrane of intestinal enterocytes, processed within the intestinal cells, and secreted across the basolateral membrane into the systemic circulation. Furthermore, because the mechanism of release from the enterocyte is different from elemental iron BioFe will be tested for its ability to treat inflammatory mediated iron deficiency in rodents to position itself to be clinically tested in individuals with ID resulting from chronic inflammation which is a significant clinical problem that BioFe can address.

铁缺乏症（ID）是全球最常见和最广泛的营养障碍，超过 20亿人遭受严重的负面健康影响。有一个广泛的，严重的 错误地认为口服铁补充剂在缓解ID方面是安全有效的;然而，在最近的一项研究中， 科克伦回顾了67项临床试验，服用口服铁补充剂的妇女只有38% 与安慰剂相比，治疗结束时ID的风险降低。此外，这些主题 副作用风险增加114%，其中绝大多数与 胃肠道（GI）紊乱。目前治疗ID的护理标准涉及铁盐 或最近的铁纳米颗粒，其在胃中降解并释放元素 铁. SideroBiosciences开发了一种颠覆性技术， 修饰以表达称为BioFe的H-铁蛋白：铁复合物。使用H- 铁蛋白;铁复合物植根于模仿母乳中的铁输送，并利用营养 酵母提供了一个容易获得的和经济的平台，用于营销和消费， 许多不同的文化和年龄组。BioFe中的铁蛋白：铁复合物特别是H- 铁蛋白将其与L-铁蛋白或植物铁蛋白区分开来，这两种铁蛋白都取得了有限的成功， 铁补充剂，因为它们在肠道中降解以释放铁，从而使用铁。 与铁盐相同的途径进入肠细胞，因此它们的性能最多类似于铁盐。 铁盐BioFe已在啮齿类动物、非人类灵长类动物和人类中成功进行了测试 （包括STTR资助的研究）。而元素铁的吸收和分泌， 肠上皮细胞的膜被相对较好地描述，受体， 铁蛋白的转运蛋白和调节机制：铁复合物尚未被发现。 介绍了在与潜在营销合作伙伴的多次讨论中，SideroBiosciences 一直询问更多关于铁蛋白如何进入的细节;铁复合物进入 身体不同于铁盐。为了解决这些问题，我们提供了 令人兴奋的试点数据，以追求在这个应用程序，将询问机制， 铁蛋白：铁复合物通过肠上皮细胞的顶膜转运， 在肠细胞内加工，并通过基底外侧膜分泌到 体循环此外，由于肠上皮细胞的释放机制是 与元素铁不同，BioFe将测试其治疗炎症介导的能力， 铁缺乏在啮齿类动物中定位，以在ID个体中进行临床测试， 慢性炎症是BioFe可以解决的重要临床问题。