Lund, April 18, 2024/Lund University/ — A treatment that has reduced plaque development in mice has now been tested in people with psoriasis. Jan Nilsson at Lund University is one of the researchers behind the clinical study that showed a reduced inflammation of the coronary arteries, which in turn may reduce the risk of dying from a heart attack. People with diabetes may also benefit from the treatment in the future.
Cardiovascular researcher Jan Nilsson is also a Senior Consultant at Skåne University Hospital in Sweden. During his professional life, he has come into contact with many patients with cardiovascular disease who, despite receiving treatment, receive another heart attack or stroke or die in connection with these events.
“We can reduce the risk of another heart attack or stroke with about 40 percent with today’s treatment methods, but we cannot reduce the risk more than that. A reason to this is that the treatment we provide is focused on treating risk factors for cardiovascular disease, such as high blood pressure and cholesterol. We still lack a treatment that targets the disease process, which means that dangerous fats accumulate in the blood vessel walls, cause inflammation, and leads to atherosclerosis,” says Jan Nilsson, senior professor of experimental cardiovascular research at Lund University Diabetes Centre.
Antibody that reduces atherosclerotic plaques
It is well known that LDL particles (low density lipoprotein) stick inside the vessel wall, where they are oxidised. This oxidation of LDL causes inflammation in the coronary arteries is a critical step in the formation and progression of atherosclerotic plaques. Plaques that rupture can cause a heart attack or stroke.
For several years, Jan Nilsson’s research group has conducted key research on Orticumab, an antibody against oxidised LDL that has reduced vascular inflammation and plaque development in animals. The treatment has now been tested in patients with psoriasis, who have an increased risk of developing cardiovascular disease. Jan Nilsson is one of the researchers behind the study, which was conducted by the company Abcentra in the United States. The results were recently published in the journal Cardiovascular Research.
May reduce risk of mortality
A total of 77 participants with psoriasis were recruited to the clinical study. The 60 participants who completed the study received either treatment with the antibody Orticumab or placebo for twelve weeks. The effect of the treatment was evaluated with a method that measures the degree of inflammation in the coronary vessel wall.
The researchers saw a reduced inflammation of the coronary arteries in participants with a high degree of inflammation who received Orticumab.
To assess the clinical significance, an algorithm that assesses the risk of a cardiac-related death over a period of eight years was used. The pilot study showed that treatment with the antibody reduced the predicted risk of dying from a heart attack with 50 percent in the group with a high degree of coronary inflammation. The calculated risk reduction is in addition to the risk reduction that the patients will receive from the other medications that they are taking.
“We believe that this is an important finding that provides increased evidence that oxidised LDL is central to the disease process. At the same time, this is a small pilot study and we need to confirm the results in larger studies. I am involved in the planning of such a study with Abcentra,” says Jan Nilsson, who is also chief scientific officer at the company Abcentra.
Patients with diabetes
If the results can be confirmed in larger studies, the treatment may for example be given in the form of injections to patients who are at risk of developing a new heart attack. People with diabetes may also benefit from such treatment in the future.
“Diabetes is sometimes detected when a patient receives treatment for a heart attack. We already know that people with type 1 diabetes and type 2 diabetes have small particles of LDL that penetrate the vessel wall more easily and they also oxidise more easily. Therefore, vascular inflammation caused by oxidised LDL is considered to be a particularly important factor in the development of cardiovascular disease in people with diabetes,” says Jan Nilsson.
Link to the press release from Abcentra and Caristo (abcentra.com)
LDL and Orticumab
Jan Nilsson’s research group has studied the role of the immune system in the development of coronary inflammation and atherosclerotic plaques. Their studies have shown that antibodies are formed against oxidised LDL. The research team has then developed human antibodies in collaboration with a company. These antibodies attach to oxidised LDL. The antibodies are recognised by macrophages, which then resolve the ongoing inflammation.
LDL stands for low density lipoprotein and is often referred to as “bad cholesterol” because it can cause cardiovascular disease if there is too much of it. In addition to cholesterol, LDL particles also contain other fats and protein. It is mainly other fats, so called phospholipids, and protein that become oxidised.
