Repair Bio’s gene therapy rapidly reverses atherosclerosis in mice

Company eyes clinical trials of mRNA therapy targeting intracellular free cholesterol after receiving ‘favorable’ pre-IND feedback.

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 LNP-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 lipid nanoparticle (LNP)-messenger RNA (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.”

Beyond atherosclerosis, Repair Bio’s gene therapy also showed promise in mouse models of metabolic dysfunction-associated steatohepatitis (MASH), with a 44% reduction in liver fibrosis observed after eight weeks of treatment.

The company revealed it received “favorable” pre-IND feedback from the FDA in March and is gearing up for further discussions as it aims to advance its therapies into clinical trials.

“Our new results in atherosclerotic mice are as impressive as the results we achieved in mouse models of MASH,” said Reason, CEO of Repair Bio. “We are preparing for mid-2024 pre-IND meetings with the FDA for treatment of the rare genetic condition of homozygous familial hypercholesterolemia, as well as the treatment of atherosclerosis more generally. Our LNP-mRNA therapy is applicable in principle to the reversal of all forms of atherosclerosis.”