Our technology makes use of apo A-I linked to an Fc of the immunoglobulin G family.  This can allow for a longer half-life of apo A-I.  The opposite end of the Fc is linked to a rescue enzyme.  One of the first compounds we have developed contains PON-1 as the rescue enzyme.  Since the Fc naturally dimerizes, the resulting therapeutic compounds contain two molecules joined in the CH3 domain of the Fc.  The presence of apo A-I provides reverse cholesterol transport activity and allows for targeting of rescue enzymes to the central nervous system.

 

Lipid free apo A-I has a short half-life which limits its ability to be used therapeutically.  Manufacturing of apo A-I mimetics typically involves a burdensome process of loading with phospholipid mixtures to help with this issue.  Previous clinical trials in humans with apo A-I mimetics have been hampered by difficulty in manufacturing.  One of the goals of our technology is to overcome this barrier.  Furthermore, not only are we increasing levels of apo A-I, but we are increasing its half-life, which could potentially decrease the frequency of treatments needed.  This is an advantage that other attempts in this field have not incorporated to this extent.

 

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