BioFe Mechanism of Action for the treatment of iron deficiency anemia

缺铁(ID)是世界上最常见和最普遍的营养失调，有超过 20亿人遭受严重的健康负面影响。有一种广泛的、严重的 误认为口服铁质补充剂在缓解糖尿病方面是安全有效的；但在最近的一项调查中 Cochrane回顾了67项临床试验，服用口服铁质补充剂的女性仅有38% 与安慰剂相比，治疗结束时ID的风险降低。此外，这些受试者有 副作用风险增加114%，其中绝大多数与 胃肠(GI)紊乱。目前治疗糖尿病的标准是铁盐。 或最近在胃中降解并释放元素的铁纳米颗粒 铁制的。西德罗生物科学公司开发了一种由营养酵母组成的颠覆性技术 修饰后表达一种H-铁蛋白：称为生物铁的铁复合体。使用H-的概念 铁蛋白；铁复合体植根于模仿母乳中的铁输送，并使用营养 酵母通过以下方式提供了一个易于访问且经济实惠的营销和消费平台 许多不同的文化和年龄段。生物铁中的铁蛋白：铁的络合物特别是H- 铁蛋白与L-铁蛋白或植物铁蛋白-不同，这两种铁蛋白在 铁补充剂，因为它们在肠道中被降解以释放铁，从而利用 进入肠道细胞的途径与铁盐相同，因此它们的表现充其量类似于 铁盐。生物铁已在啮齿动物、非人类灵长类动物和人类身上成功测试 (包括一项由STR资助的研究)。而元素铁的吸收和分泌 对肠上皮细胞膜的描述相对较好，受体(S)， 转运蛋白(S)，和调节机制(S)对于H-铁蛋白：铁的络合物还没有 描述。在与潜在营销合作伙伴的多次讨论中，SideroBiosciences已经 一直被问及有关铁蛋白；铁复合体是如何进入 身体不同于铁盐。因此，为了解决这些问题，我们提供了 在此应用程序中要追求的令人兴奋的试点数据，这些数据将询问 铁蛋白：铁复合体通过肠上皮细胞的顶膜运输， 在肠道细胞内加工，并通过基底膜分泌到 体循环。此外，由于从肠道细胞释放的机制是 与元素铁不同的是，生物铁将被测试其治疗炎症介质的能力 啮齿类动物的铁缺乏定位于临床检测结果为ID的个体 从慢性炎症，这是一个重大的临床问题，生物铁可以解决。

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.