Immune Therapies to Reduce Atherosclerosis

Via EurekAlert!: "injecting cardiovascular disease (CVD) patients with vaccines and monoclonal antibodies to combat atherosclerosis could soon change the treatment landscape of heart disease. Both approaches [can] be considered truly ground breaking since for the first time they target the underlying cause of CVD. ... with phase 2a trials on recombinant antibodies currently ongoing, [such] treatments could soon become a clinical reality. ... If all goes well, the first in class of these treatments could be licensed within four to five years ... Established therapies against atherosclerosis almost exclusively focus on risk factor modification - that is reduction of dyslipidaemia, hypertension and hyperglycaemia. ... It was in the early 1990s that identification of antibodies against oxidised low density lipoproteins (LDL) in artery plaques, first gave rise to the concept that CVD might be an autoimmune disease where the immune system attacks oxidised LDL. ... Since it is impractical to develop vaccines based on oxidised LDL (due to difficulty of standardising the particle) [researchers] looked to identify structures within the oxidised LDL that triggered the desired protective response. ... The team were able to identify three [peptides], which when formulated with a carrier and adjuvant, reduced development of atherosclerosis in mice by 60 to 70%. ... Further along the development pathway, and already in clinical trials, is an altogether different immune approach involving injection of antibodies directly targeting oxidised LDL. ... The rationale is that since oxidised LDL plays a major role in the development of atherosclerotic plaques and harmful inflammatory processes, directly targeting oxidised LDL should prevent plaque formation and reduce inflammation ... Preclinical studies show that administration of the BI-204 monoclonal antibody [reduced] the formation of atherosclerotic plaques and plaques already present by 50%. In the phase I study, which took place in 80 healthy volunteers with elevated levels of LDL, BI-204 was found to be safe and well tolerated. Now for the current phase 2a double blind [study], BI-204 is being delivered intravenously to 144 patients with stable coronary artery disease in addition to standard care."


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