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A Spanish research institute, in conjunction with a German research center, has discovered 18 antibodies that show reactivity against the atherosclerotic plaque, so that, they could be used for the diagnosis of atherosclerosis. Moreover, the use of one specific antibody, A12 antibody, prevents the progression of the disease and reduces the level of free circulating cholesterol and LDL. They are looking for partners, with no preferred location, to establish a license agreement.
Atherosclerosis is a chronic inflammatory disease that underlies thrombosis and cardiovascular events, but it can remain asymptomatic for long periods of time. A Spanish research institute, supported by a German research center, has developed a set of antibodies targeting this illness.
Atherosclerosis is considered the most frequent cause of death in western countries, doubling the deaths caused by cancer. This is because atherosclerosis is responsible for many other fatal vascular diseases, such as stroke (if atherosclerotic plaque occurs in the carotid artery) or myocardial infarction (if it occurs in the coronary arteries). In Spain, atherosclerosis is responsible for 124,000 deaths each year.
The presence of antibodies in the atherosclerotic plaque was described decades ago, and the connection between autoimmunity and atherosclerosis is well accepted. However, the immunogenic trigger and the impact of the antibody immune response during atherosclerosis are not well understood.
Therefore, researchers are studying solutions to replace them.
An inflammatory response is triggered during atherosclerosis. This response is due to the retention and oxidation of low-density lipoprotein (LDL) at the vessel sub-endothelium space. In addition, the adaptive arm of the immune response is known to be critical during atherosclerosis. Distinct functions have been attached to B cells and the antibody immune response during atherosclerosis development.
Antibodies are molecules produced by the body throughout the life of the individual. They have composed of a heavy chain dimer and two light chains. They are now routinely used as a diagnostic tools in the clinic and in research to investigate pathological signaling. More recently, antibodies have been utilized for another application – therapy. Antibody therapies are relatively limited to the cardiovascular system. There are some antibodies for treating cardiovascular disorders like coronary artery disease, heart failure, and transplant. In addition, there are antibodies that can be used as therapeutic agents in atherosclerosis, such as VCAM-1 (vascular cell adhesion protein 1) antibodies or anti-CD20 antibody, but they do not have very specific reactivity patterns against the atherosclerotic plaque.
The researchers have performed a high-throughput single-cell analysis of the antibody repertoire associated with atherosclerosis. They sequenced more than 1700 antibodies from LDLR-/- mice with high-fat diet (HDF) and control mice, 18 of them showed reactivity against atherosclerotic plaques. They found that one such antibody, A12, binds to atherosclerotic plaques in LDLR-/- HFD mouse model and in human carotid atherosclerosis lesions. Importantly, the researchers have found that the A12 antibody recognizes a certain protein whose distribution is altered during atherosclerosis. The levels of this protein are increased in the plasma of atherosclerotic mice and of humans with atherosclerosis. In addition, it was proved that the treatment of LDLR-/- HFD mice with infusions of A12 antibody delays atherosclerosis progression and reduces circulating free cholesterol and LDL. These findings open the way A12 antibody as a very promising clinical tool in cardiovascular disease, both for the diagnosis and for the treatment of atherosclerosis.
The research centers are looking to establish a license agreement with a biotech or pharmaceutical company working in alternative diagnostic methods or/and treatments for cardiovascular diseases, preferably in atherosclerosis.
• A12 antibody and the additional 17 antibodies have a very specific reactivity pattern against the atherosclerotic plaque. These patterns differ from traditional markers of this disease, such as anti-oxLDL (oxidized low-density lipoprotein).
• These antibodies show specific reactivity against the atherosclerotic plaque from the early stages of the disease, so they can be used as diagnostic agents for the early detection of the disease before the patients have symptoms. In addition, they can be used as a tool to study the physiological processes of atherosclerosis.
• These antibodies were identified from LDLR-/- HFD atherogenic mice during the progression of the disease, thus, no toxicity is expected when used as a therapeutic agent.
• A12 antibody allows the detection of atherosclerotic plaque in vivo. Functional in vivo experiments showed that A12 antibody treatment decreases the extension of atheroma plaque in LDLR-/- HFD mice.
Tested in animal models.
EP patent filed, suitable for international extension
The research centers are seeking for biotech or pharmaceutical companies working in new diagnostic methods or/and treatments for cardiovascular diseases, particularly atherosclerosis, for out-licensing the patent. The partner would complete all the steps needed to commercialize the technology.