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As some of you know, Repair Biotechnologies is the company I co-founded with Bill Cherman back in 2018. We’ve been working on an approach to reverse atherosclerosis for much of that time, and matters have progressed through the stage of great data in mice to present preparations for a pre-IND meeting with the FDA. While excess cholesterol has long been understood to be important to the development of atherosclerosis, it turns out that circulating cholesterol bound to LDL particles is less important than the amount of localized excess cholesterol in the liver and blood vessel walls.
Any localized excess of cholesterol can overwhelm the ability of cells to reduce uptake or store cholesterol in either the cell membrane or in esterified droplets. The resulting free cholesterol inside cells is toxic. The gene therapies developed by the Repair Biotechnologies scientists put in place novel protein machinery that can selectively and safely break down this excess free cholesterol without harming the cholesterol necessary to cell function. This can, for example, protect macrophages from becoming foam cells when exposed to excessive cholesterol. It can also put a halt to dysfunction in liver cells affected by the excess cholesterol present in a fatty liver.
Repair Biotechnologies’ gene therapy rapidly reverses atherosclerosis in mice
Gene therapy company Repair Biotechnologies has revealed promising preclinical results that demonstrate its technology rapidly reverses the progression of atherosclerosis in mouse models. The company says the development holds potential for treating both atherosclerosis and a rare genetic condition called familial hypercholesterolemia, in humans.
Atherosclerosis is a condition characterized by the buildup of plaque in arteries, eventually blocking blood flow, and contributing significantly to heart disease, stroke, and death. In experiments, scientists at Repair Biotechnologies treated atherosclerotic mouse models with the lipid nanoparticle (LNP)–messenger RNA (mRNA) therapy over a six-week period, with promising results.
Both groups of mice, one representing a general population model for atherosclerosis, and another modeling familial hypercholesterolemia, exhibited significant reductions in plaque buildup. Specifically, the atherosclerotic mice showed a 19% drop in plaque lipids and a 23% increase in plaque collagen, indicating stabilization of vulnerable plaque. The mice with familial hypercholesterolemia experienced a 17% reduction in plaque obstruction in the aortic root, alongside improved cardiovascular health demonstrated by increased treadmill capacity.
Based in Syracuse, New York, Repair Bio is developing LNP-mRNA therapies targeting a range of health conditions. Unlike traditional therapies that focus on reducing LDL-cholesterol levels in the bloodstream, the company’s therapy targets intracellular free cholesterol, which is toxic to cells and contributes to the development of numerous conditions. Repair Bio’s approach leverages its cholesterol degrading platform technology to safely break down excess free cholesterol within cells.
“Unfortunately statins and PCSK9 inhibitors that reduce LDL-cholesterol in the blood exhibit little ability to reduce the size of established atherosclerotic lesions,” said Mourad Topors, CSO at Repair Bio. “Our studies in severely atherosclerotic mice demonstrate that LDL-cholesterol is the wrong target if the goal is the outright regression of plaque and dramatic reduction in risk of cardiovascular events. Instead, clearance of intracellular free cholesterol can potentially achieve these goals.”