(Press-News.org) London -- New strategies injecting cardiovascular disease (CVD) patients with vaccines and monoclonal antibodies to combat atherosclerosis could soon change the treatment landscape of heart disease. Both approaches, Professor Jan Nilsson told delegates at the Frontiers in CardioVascular Biology (FCVB) 2012 meeting, can be considered truly ground breaking since for the first time they target the underlying cause of CVD. The FCVB meeting, organised by the Council on Basic Cardiovascular Science (CBCS) of the European Society of Cardiology (ESC), held 30 March to 1 April at the South Kensington Campus of Imperial College in London.
"People at high risk of MI are likely to be the first candidates for immune approaches. Such treatments, since they've totally different modes of action, could be used in addition to the current therapies," explained Nilsson, who is professor of Experimental Cardiovascular Research at Lund University, Sweden, and a key player in the development of immune treatments.
Speaking at the session "Atherosclerosis and the immune system: Expanding beyond inflammation"¹, Nilsson said that with phase 2a trials on recombinant antibodies currently ongoing in the US and Canada and results expected to be announced Quarter IV 2012, 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," he added.
Undoubtedly there is an urgent need for new approaches to tackle CHD, a condition that kills two million people across Europe each year. Established therapies against atherosclerosis almost exclusively focus on risk factor modification – that is reduction of dyslipidaemia, hypertension and hyperglycaemia. "Existing treatments only reduce the risk of patients experiencing a CVD event by 40%. Although such results are encouraging, it shouldn't be forgotten that 60% of CVD events continue to occur," said Nilsson.
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. To test this hypothesis Nilsson and colleagues conducted experiments immunizing rabbits with high blood cholesterol with their own oxidised LDL. "We had anticipated that immunization would result in the atherosclerosis becoming more aggressive, but to our initial disappointment found that immunization appeared to be activating protection against atherosclerosis. At the time this made no sense to us at all," he recalled.
The team subsequently discovered that through serendipitous use of an adjuvant (agent added to vaccines to increase the immune response) they had in fact stumbled upon a way to shift the T cells from pro-inflammatory Th1 responses towards protective Th2 and regulatory T cell responses. "This had the overall effect of dampening down inflammation and reducing the plaque severity," said Nilsson.
Since it is impractical to develop vaccines based on oxidised LDL (due to difficulty of standardising the particle) Nilsson looked to identify structures within the oxidised LDL that triggered the desired protective response. Working with Prediman Shah, from Cedars-Sinai Heart Institute (Los Angeles, CA), the team screened a number of different apolipoprotein (apo) B peptides (the only protein permanently associated with LDL) sequences. The team were able to identify three 20 amino acid long apo B peptides, which when formulated with a carrier and adjuvant, reduced development of atherosclerosis in mice by 60 to 70%.
The resulting CVX-210 vaccine, currently in development by CardioVax, involves one of these three amino acid fragments (residues 3136 to 3155). CardioVax are currently awaiting FDA clearance to start phase 1 clinical trials with the vaccine, which will be given subcutaneously. Also in development is a second vaccine using the same amino acid sequence that has been formulated in a way that makes it possible to give intranasally.
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," explained Nilsson.
Preclinical studies show that administration of the BI-204 monoclonal antibody, developed jointly by BioInvent and Genentech, 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 GLACIER (Goal of oxidised Ldl and Activated maCrophage Inhibition by Exposure to a Recombinant antibody) study, BI-204 is being delivered intravenously to 144 patients with stable coronary artery disease in addition to standard care. The study, which is taking place at 20 centres in the US and Canada, has been designed to demonstrate reduction in inflammation in the carotid artery quantified by FDG-PET imaging (18Fluoro-2-deoxyglucose positron emission tomography) at weeks four and 12 following initiation of treatment. At the beginning of March, the companies announced that patient recruitment was completed.
Looking to the future, Nilsson said it was unlikely that either the monoclonal antibodies or vaccine would be given as "one off jabs" during childhood against CVD. "Both these treatments are far more like drugs – to be effective they'd need to be given long term. The antibody therapy in particularly is likely to be expensive so you could probably only afford to give it to high risk populations rather than everyone," he said.
###Reference
1. Session Atherosclerosis and the immune system –Expanding beyond inflammation.
30 March 2012. 14.30- 16.00. Clore Lecture Theatre.
Authors: ESC Press Office
Tel: 33-4-92-94-86-27
Fax: 33-4-92-94-86-69
Email: press@escardio.org
About the European Society of Cardiology (ESC)
The European Society of Cardiology (ESC) represents more than 75,000 cardiology professionals across Europe and the Mediterranean. Its mission is to reduce the burden of cardiovascular disease in Europe.
About Frontiers in CardioVascular Biology (FCVB)
Frontiers in CardioVascular Biology (FCVB) is a biennial meeting organised by the ESC Council on Basic Cardiovascular Science (CBCS) together with eight ESC Working Groups and six European basic science societies (Sister Societies).
The ESC working groups include Atherosclerosis and Vascular Biology; Cardiac Cellular Electrophysiology; Cardiovascular Pharmacology and Drug Therapy; Cellular Biology of the Heart; Coronary Pathophysiology and Microcirculation; Development, Anatomy and Pathology; Myocardial Function; and Thrombosis. The sister societies include European Vascular Biology Organization; International Society for Heart Research;-European Section, European Council for Cardiovascular Research; European Society for Microcirculation; European Atherosclerosis Society; and Association for European Cardiovascular Pathology.
Immune therapies: The next frontier in battle against atherosclerosis
2012-04-02
ELSE PRESS RELEASES FROM THIS DATE:
Children who develop asthma have lung function deficits as neonates
2012-04-02
Children who develop asthma by age seven have deficits in lung function and increased bronchial responsiveness as neonates, a new study from researchers in Denmark suggests.
"Previous research on the relationship between neonatal lung function and the development of asthma has been conflicting," said lead author Hans Bisgaard, MD, DMSci, professor of pediatrics at the University of Copenhagen and head of the Danish Pediatric Asthma Centre. "Our study shows that children with asthma by age seven already had significant airflow deficits and increased bronchial responsiveness ...
CDC study forges link between depression and sleep apnea
2012-04-02
DARIEN, IL – Obstructive sleep apnea and other symptoms of OSA are associated with probable major depression, regardless of factors like weight, age, sex or race, according to a new study from the Centers for Disease Control and Prevention. There was no link between depression and snoring.
"Snorting, gasping or stopping breathing while asleep was associated with nearly all depression symptoms, including feeling hopeless and feeling like a failure," said Anne G. Wheaton, PhD, lead author of the study. "We expected persons with sleep-disordered breathing to report trouble ...
Middle-of-the-night PCIs do not adversely affect success of next-day procedures
2012-04-02
A single-center study found that percutaneous coronary intervention (PCI) procedures performed during the middle of the night do not adversely affect the safety and effectiveness of procedures performed the next day by the same operator. Findings now available in Catheterization and Cardiovascular Interventions, a journal published by Wiley-Blackwell on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI), show late night work while on call does not worsen performance of the interventionist doing PCIs the next day.
Studies have shown that sleep ...
Making mice comfy leads to better science, Stanford researcher says
2012-04-02
STANFORD, Calif. — Nine out of 10 drugs successfully tested in mice and other animal models ultimately fail to work in people, and one reason may be traced back to a common fact of life for laboratory mice: they're cold, according to a researcher at the Stanford University School of Medicine.
Laboratory mice, which account for the vast majority of animal research subjects, are routinely housed in chilly conditions, which may affect their well-being as well as the outcome of research studies, said Joseph Garner, PhD, associate professor of comparative medicine.
"If you ...
Starvation linked to greater risk of cardiac complications
2012-04-02
London -- Russians born during the Leningrad Siege in World War II, which was responsible for some of the greatest losses of civilian life in history, are giving scientists new strategies to identify people who experienced intrauterine growth restriction (IUGR) and starvation during childhood at greatest risk of developing long term heart complications. The abstract study¹, presented at the Frontiers in CardioVascular Biology (FCVB) meeting, in London, UK, 30 March to 1 April 2012, makes use of a unique population of people exposed to extreme starvation both as foetuses ...
Clocking an accelerating universe: First results from BOSS
2012-04-02
Some six billion light years ago, almost halfway from now back to the big bang, the universe was undergoing an elemental change. Held back until then by the mutual gravitational attraction of all the matter it contained, the universe had been expanding ever more slowly. Then, as matter spread out and its density decreased, dark energy took over and expansion began to accelerate.
Today BOSS, the Baryon Oscillation Spectroscopic Survey, the largest component of the third Sloan Digital Sky Survey (SDSS-III), announced the most accurate measurement yet of the distance scale ...
Benefits of taking Fido to work may not be far 'fetched'
2012-04-02
RICHMOND, Va. (March 30, 2012) – Man's best friend may make a positive difference in the workplace by reducing stress and making the job more satisfying for other employees, according to a Virginia Commonwealth University study.
Stress is a major contributor to employee absenteeism, morale and burnout and results in significant loss of productivity and resources. But a preliminary study, published in the March issue of the International Journal of Workplace Health Management, found that dogs in the workplace may buffer the impact of stress during the workday for their ...
Volcanic plumbing exposed
2012-04-02
Two new studies into the "plumbing systems" that lie under volcanoes could bring scientists closer to predicting large eruptions.
International teams of researchers, led by the University of Leeds, studied the location and behaviour of magma chambers on the Earth's mid-ocean ridge system - a vast chain of volcanoes along which the Earth forms new crust.
They worked in Afar (Ethiopia) and Iceland - the only places where mid-ocean ridges appear above sea level. Volcanic ridges (or "spreading centres") occur when tectonic plates "rift" or pull apart. Magma (hot molten ...
Some corals like it hot: Heat stress may help coral reefs survive climate change
2012-04-02
A team of international scientists working in the central Pacific have discovered that coral which has survived heat stress in the past is more likely to survive it in the future.
The study, published today in the journal PLoS ONE, paves the way towards an important road map on the impacts of ocean warming, and will help scientists identify the habitats and locations where coral reefs are more likely to adapt to climate change.
"We're starting to identify the types of reef environments where corals are more likely to persist in the future," says study co-author Simon ...
The electronic nose knows when your cantaloupe is ripe
2012-04-02
Have you ever been disappointed by a cantaloupe from the grocery store? Too ripe? Not ripe enough? Luckily for you, researchers from the University of California, Davis might have found a way to make imperfectly ripe fruit a thing of the past. The method will be published on March 30 in the Journal of Visualized Experiments (JoVE).
"We are involved in a project geared towards developing rapid methods to evaluate ripeness and flavour of fruits," said paper-author Dr. Florence Negre-Zkharov. "We evaluated an electronic nose to see if it can differentiate maturity of fruit, ...