HDL注入はコレステロールを迅速に血管外へ移動させる

静脈内HDLコレステロール蛋白注入はその後の心筋梗塞リスクを低下させる可能性がある
IV infusion of HDL cholesterol protein may lower risk of subsequent myocardial infarction
2012年American Heart Association学会で発表された小規模な早期スタディの結果、研究者らは、HDL内の主たる蛋白の静脈内注入はコレステロールを狭窄動脈から排出させる身体の能力を増強させるようであり、その後の心筋梗塞（MI）リスクを軽減させる可能性があることを発表した。このスタディには血管内投与可能な自然の、コレステロールを動脈や他の組織から肝臓へ転送し排出させるHDL粒子のキー蛋白である人型アポリポプロテインA-1（Apo-A-1）CSL112を用いた。研究者らは57人の健康なボランティアに対し、5～135mg/kgの用量のCSL112を単回注射し、それに対する反応としてのコレステロールの移動のマーカーを調査した。プラセボ注射と比較し、細胞からのコレステロール排出は速やかに増加した（ベースラインより最大270%）。コレステロール低下に関与するHDLの亜分画preβ1-HDLは劇的に増加した（ベースラインより最大3600%）。全体的に、CSL112は研究者らが期待したのと同等またはそれ以上に作用し、全ての変化はコレステロール逆転送活性の期待された上昇と合致していた。この方法が臨床試験で成功すれば、より緩徐にHDLコレステロールを上昇させる薬剤と比較しこの薬剤は近い将来のMI高リスクを軽減する可能性がある。
Full Text

An intravenous infusion of high-density lipoprotein (HDL) cholesterol could reduce the risk of a subsequent myocardial infarction (MI), researchers reported at the American Heart Association's Scientific Sessions 2012.

In a small, early study, researchers noted that an intravenous infusion of the chief protein in high-density lipoprotein (HDL) seems to rapidly boost the body's ability to move cholesterol out of occluded arteries.

In the days and weeks after a myocardial infarction or angina, patients are at high risk of another attack. Standard medications, such as aspirin and anti-platelet drugs, prevent clotting but don't help eliminate the underlying cause — cholesterol that has built up in artery plaque.

Other HDL drugs, such as niacin and fibrates, which do attack the underlying cause, gradually raise HDL and may prevent MIs years after the start of therapy.

The study involves CSL112, an infusible and natural human formulation of Apolipoprotein A-1 (ApoA-1), the key protein in HDL particles that transports cholesterol from arteries and other tissues into the liver for disposal.

"In a current multi-center study, CSL112 will be administered as a short series of weekly IV infusions initiated shortly following a heart attack or heart-related chest pain," said Andreas Gille, M.D., Ph.D., lead author of the study and Head of Clinical and Translational Science Strategy at CSL Limited in Parkville, Australia. "Our aim is to address a significant gap in acute coronary syndrome management by reducing the high risk of early recurrent events."

Researchers studied markers of cholesterol movement in response to a single infusion of CSL112 at doses ranging from 5 to 135 mg/kg in 57 healthy volunteers.

Compared with a placebo infusion, they found:

  • Cholesterol extraction from cells rose immediately (up to 270 percent from baseline).
  • PreBeta1-HDL, a subfraction of HDL involved in cholesterol elimination, increased dramatically (up to 3,600 percent from baseline).

"Overall, CSL112 behaved as well or better than we expected and all the changes are consistent with the desired elevation in reverse cholesterol transport activity," Gille said. "We did not observe any unfavorable changes in the low density lipoprotein or 'bad' cholesterol-related biomarkers tested."

The safety and behavior of CSL112 in patients with stable heart disease is being evaluated in a multi-center trial.

Co-authors are Rachael Easton, M.D., Ph.D.; Samuel D. Wright, Ph.D.; and Charles L. Shear, Dr.P.H. Author disclosures are on the abstract.

CSL Limited funded the study.