Technology ID

High Density Lipoprotein Targeting Protease Inhibitor Peptide for the Treatment of Alpha-1-antitrypsin (A1AT) Deficiency

Lead Inventor
Remaley, Alan (NHLBI)
Gordon, Scott (University of Kentucky)
Therapeutic Areas
Development Stages
Pre-clinical (in vivo)
Lead IC

This technology includes a novel concept and design for a lipoprotein targeting protease inhibitor for the treatment of Alpha-1-antitrypsin (A1AT) deficiency. A1AT deficiency occurs in about 1 in 2500 individuals in the United States and Europe, and people with this condition develop severe liver disease and emphysema/chronic obstructive pulmonary disease (COPD). Current treatment involves intravenous infusion of purified human A1AT protein, which is very expensive and only modestly effective. A recent study has demonstrated improvement in A1AT treatment effectiveness in a mouse model of emphysema by pre-incubating A1AT with high density lipoprotein (HDL) particles prior to infusion. This resulted in improvements in lung morphology and inflammatory markers in the lung compared to A1AT treatment alone. The mechanism for this improvement in function of A1AT when bound to HDL is believed to be increased trafficking of A1AT to the lung. Our invention of a lipoprotein targeting protease inhibitor peptide represents several significant advances upon these existing methods.

Commercial Applications
Therapy for the treatment of A1AT deficiency.

Competitive Advantages
This approach is expected to provide improved efficacy over the current standard of care (A1AT infusion) because this design is a small molecule of about 2.5 kDa, much smaller than the full-length protein (52 kDa). An HDL particle can generally accommodate only one molecule of A1AT, whereas many copies of our VitE-PEG-AAPV peptide can reside on an HDL particle providing a significant increase in potency.
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