We will perform a clinical study to test a novel, patented medical food to manage iron deficiency anemia. The project is significant because it addresses the number one nutritional disorder in the world; and a health problem on the global scale that is second only to tuberculosis in cost worldwide. Estimates are that approximately 2 billion people, more than 30% of the population, suffers from iron deficiency anemia. Iron deficiency affects infants, young children and women of child bearing age and is increasing in significance among the elderly. The implications of iron deficiency anemia range from (IDA) fatigue, to cardiomyopathy to increased risk of ADHD in children and cognitive decline in the elderly. Oral iron therapy is first line treatment for patients with IDA. The current treatment strategies for iron deficiency are inadequate for a number of reasons chief among them is poor absorption. Adverse events (AE) are reported in at least 40% of individuals receiving oral iron and include significant GI discomfort, nausea, epigastric discomfort, pain, vomiting and constipation. These AE's result in low treatment persistency. We are proposing a novel iron delivery system that is based on our discovery that iron can be taken up by a number of organs including the brain via H-ferritin. We hypothesized that H-ferritin expressed in nutritional yeast could be a significant source of oral iron. We have performed successful preclinical studies in two animal models. Our product is innovative on a number of levels. First of all, our choice to use the H-subunit of ferritin is novel and differentiates our product from those using plant ferritins which are more similar to the L-subunit of ferritin. We and others have shown that L-ferritin is not readily taken up by organs in the body. Absorption of iron from plant ferritin is n better than from iron salts which are the current standard of care. Secondly, our product can be produced economically in large scale and is grown in controlled laboratory conditions allowing for consistent quantities of iron and ferritin. This approach also differentiates our product from the bioagriculture approach where the amount of iron in the soil is inconsistent and cannot be controlled. Plant ferritin can also accumulate metals from the soil other than iron including potentially toxic metals such as cadmium. In addition, plants have phytates that limit iron absorption. Thus this project is innovative because we have a novel approach to make iron more bioavailable in a food that is commonly consumed directly by many cultures. By providing iron in human ferritin, we are providing a safe, natural and efficient mechanism for delivering iron in the diet; an approach that mimics iron delivery from breast milk. In this study, we propose a Phase 1b ascending dose trial in humans to determine safety and tolerability of our product. Clinical data are expected to generate significant interest among those in the functional food and medical foods industry with whom we can partner to provide the world with a treatment for iron deficiency.
Public Health Relevance Statement: Public Health Relevance: Over 2 billion people, more than 30% of the world's population, suffer from iron deficiency. Current methods of treatment are inadequate. The relevance of this application to public health is that iron deficiency anemia is the number one nutritional disorder in the world. We will test patented novel medical food for management of iron deficiency anemia in a Phase 1b human trial. Our product is a nutritional strain of yeast that has been biotechnologically modified to express the human H-ferritin protein; thereby mimicking the mechanism by which iron is transported from breast milk to nursing infants. Yeast is consumed by most cultures around the world thus our delivery mechanism can be considered safe, affordable and in an acceptable form that will encourage consumption.
Project Terms: absorption; Address; Adverse effects; Adverse event; Affect; Agreement; Anemia; Animal Model; Attention deficit hyperactivity disorder; base; Bioavailable; Blood - brain barrier anatomy; Bolus Infusion; Brain; Cadmium; Cardiomyopathies; Child; Chronic; Clinical Data; Clinical Research; commercial application; commercialization; Constipation; Consumption; Contracts; cost; Data; design; Diet; dietary supplements; Discipline of Nursing; Dizziness; Dose; Dried Yeast; Elderly; Enzymes; Epigastric; Fatigue; Female of child bearing age; Ferritin; Ferrous Sulfate; Food; Food Industry; Formulation; Functional disorder; functional food; General Practitioners; Government; H ferritin; Health; Health Food; Heart; Hospitals; Human; Human body; human data; Human Milk; human subject; Impaired cognition; improved; indexing; Individual; Infant; Injection of therapeutic agent; innovation; Inorganic Iron Compounds; interest; Internet; Iron; iron deficiency; Iron deficiency anemia; Kidney; Knowledge; L Forms; L-ferritin; Laboratories; Legal patent; Letters; Licensing; Liver; Malnutrition; Marketing; Measures; Mediating; Medical center; medical food; meetings; Metals; Methods; Milk; Mitochondria; Mothers; Nature; Nausea; nonhuman primate; novel; novel strategies; Nutrition Disorders; Nutritional; Oral; Organ; Organic Iron Compounds; Pain; Pallor; Pathway interactions; Patients; Pharmacologic Substance; Phase; phytate; Plants; Population; pre-clinical; preclinical study; primary outcome; Production; programs; Proteins; Public Health; public health relevance; Reporting; Rights; Risk; Rodent; Safety; Salts; Scientist; Serum; Shortness of Breath; Small Business Technology Transfer Research; Soil; Source; standard of care; Symptoms; System; Technology; Testing; Toxic effect; toxic metal; treatment strategy; Tuberculosis; United Nations; Universities; Vomiting; Work; World Health Organization; Yeasts
