LIPC VARIANT IN THE TREATMENT OF HYPERCHOLESTEROLEMIA AND ATHEROSCLEROTIC CARDIOVASCULAR DISEASE

Inventors have performed a pioneer study (Figure 5) by overexpressing control eGFP, human WT and E97G LIPC in full Ldlr-/- females fed with a pro-atherogenic diet for 9 weeks, using AAV8 viruses as described before. Their results revealed that the E97G LIPC expression 1) strongly reduces plasma cholesterol levels in Ldlr-/- females; 2) potently decreases the size of aortic atherosclerotic lesions. These preliminary data support the hypothesis of a beneficial role of LIPC E97G towards the development of atherosclerosis and reinforce the need for further studies. Interestingly, they also open the prospect of new therapeutic solutions in familial hypercholesterolemia (FH) patients with partial/total LDLR deficiency. The present invention relates to a method for treating hypercholesterolemia, including homozygous and heterozygous FH, and related ASCVD in a subject in need thereof comprising administering a therapeutically effective amount of a LIPC variant to said subject in need thereof.

Keywords: Atherosclerosis, familial hypercholesterolemia, metabolic disorders, new product
Patent Application number: International Procedure (PCT) - 17 Mai 2023 - PCT/FR2023/050714
Inventors:
Di Filippo Mathilde; CARIOU Bertrand; LE MAY Cedric
Publications:
Sotin T, Ge X, Schönke M, Vince L, Thouzeau A, Frey S, Lorant V, Krul L, Pronk ACM, Lalai R, Streefland TCM, Afkir S, Dijk W, Smati S, Heijink M, Blomberg N, Giera M, Di Filippo M, Moulin P, Kooijman S, Cariou B, Rensen PCN, Le May C. A rare gain of function variant of hepatic lipase attenuates hypercholesterolaemia and atherosclerosis in mice via an LDL receptor-independent mechanism. Cardiovasc Res. 2025 Jul 8;121(7):1024-1035. doi: 10.1093/cvr/cvaf097. PMID: 40460236.

Reference:

BIO23131-T1

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Rare disease: Yes
Second indication: Yes

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