Apo A-1 Milano for Alzheimer's Disease and Atherosclerosis

Tech ID: sha482/059/470/400



Apolipoprotein A-I (ApoA-I) is the major structural protein component of high-density lipoprotein (HDL). Apolipoprotein A-I Milano (ApoA-IM), a naturally occurring Arg173 to Cys mutant of ApoA-I, was found in a small number of inhabitants of a northern Italian town. Compared to the normal gene (apolipoprotein A-1), the mutant gene (apo A-1 Milano) produces a form of HDL (high-density lipoprotein or "good" cholesterol) that provides greater protection against atherosclerosis and vascular inflammation, as well as Alzheimer’s disease.


Technology Description

Dr. Shah and his colleagues have been studying ApoA-I Milano since 1992. With developments over the years, ApoA-I Milano has been shown to reduce atherosclerosis in animal models and in a small phase 2 human trial. Dr. Shah and colleagues have recently found and validated in mouse model that a new serotype of AAV vector is more effective than the vector used before. He also has unpublished data in mouse model showing the therapeutic effects of AAV mediated gene transfer of Apo A-I Milano on atherosclerosis. His pilot work in the Alzheimer’s mouse model showed that Apo A-I Milano gene transfer had positive therapeutic effects measured by several endpoints.



• These findings can be developed into a gene therapy based on AAV delivery platform. It presents promising new treatment options for atherosclerosis and Alzheimer’s disease, where current methods have limitations and are not always effective.


Intellectual Property

Patent family includes issued patents and pending applications. Claims are directed towards AAV mediated gene transfer of ApoA-I Milano gene to treat atherosclerosis and Alzheimer’s disease.


Selected Publications 

Wang et al. Comparative effects of diet-induced lipid lowering versus lipid lowering along with Apo A-I Milano gene therapy on regression of atherosclerosis. Journal of Cardiovascular Pharmacology and Therapeutics. 2015. [LINK]


Tian et al. Comparative antiatherogenic effects of intravenous AAV8- and AAV2- mediated ApoA-I Milano gene transfer in hypercholesterolemic mice. Journal of Cardiovascular Pharmacology and Therapeutics. 2015.1, 20(1) 66-75. [LINK]

Wang et al. Bone marrow transplantation shows superior atheroprotective effects of gene therapy with apolipoprotein A-I Milano compared with wild-type apolipoprotein A-I in hyperlipidemic mice. J Am Coll Cardiol. 2006, 48(7):1459-1468. [LINK]

Patent Information:
For Information, Contact:
Wenyue Du
Senior Associate - IP Management & Licensing
Prediman Shah
Gene Therapy