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A REVOLUTION IN TREATING CARDIOVASCULAR DISEASE, APOLIPOPROTEIN A-I MILANO
Cardiovascular diseases are one of the principal causes of illness and death in industrial countries. Several factors are implicated in the development of these diseases including hereditary pre-disposition, age, smoking, diet, hypertension and hyperlipidemia; in particular high cholesterol. The total concentration of cholesterol in the blood is influenced by the absorption of cholesterol in the digestive tract, the synthesis of cholesterol from components of the diet, and the removal of cholesterol from the blood to tissues, especially the liver; and the subsequent conversion to bile acids, hormones, steroids, and bile cholesterol.
Human Apolipoprotein A-1 (Apo A-1) is the subject of intense research for its anti-atherogenic properties. The protein is found tightly associated with phospholipids and forms complexes and promotes the efflux of cholesterol from cholesterol-rich cells. A naturally-occurring mutation in Apo A-1 was discovered in a family in Northern Italy who has a very low incidence of coronary atherosclerosis, and was named Apo A-1 Milano.
Recent studies (Nissen et al. 2003) indicate that 'HDL Therapy' with infusions of a formulation (ETC-216: synthetic HDL phospholipids complex) of Apo A-1 Milano significantly reduces coronary atherosclerotic plaques by rapidly remove excess cholesterol and other lipids from artery walls to the liver for elimination, by reverse lipid transport..
Plantechno has developed transgenic rice lines expressing the variant form of the Apolipoprotein A-I (Apo A-I Milano dimer) and other oligomers. The rice lines express the Apo A-I Milano gene in seeds by using a seed-specific promoter. High expression of the protein in the dimer form, has been achieved. Currently, production of Apo A-I Milano is expensive and laborious, and repeated dosage administrations to patients are needed to sustain benefits. Plant production of Apo A-I Milano may provide a more cost-effective and safe option of producing this protein for therapeutic use.
Stage of Research or product development:
Seed increase, protein characterization, protein purification.
Patent:
Italian patent granted August 10 2006 (national and international priority date), PCT in progress.
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