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Researchers have identified a new type of regulatory blood cell that is able to combat hyperactive T-cells responsible for degenerative diseases such as multiple sclerosis (MS).

Diseases like MS occur when hyperactivity of the immune system results in a chronic state of inflammation. Scientists at BRIC, the University of Copenhagen, stimulated the regulatory blood cells and thereby reduced the level of brain inflammation and disease in a biological model. The results are published in the journal Nature Medicine.

The new blood cells belong to the group of white blood cells known as lymphocytes. A molecule called FoxA1, responsible for the cells' development and suppressive functions, is expressed by these cells.

When inserting FoxA1 into normal lymphocytes using gene therapy, the team found they were able to modify them to actively regulate inflammation and inhibit multiple sclerosis.

FoxA1-expressing lymphocytes were previously unknown. Headed by professor Shohreh Issazadeh-Navikas, the BRIC researchers examined the blood of patients with multiple sclerosis, before and after two years of treatment with the drug interferon-beta. They discovered that patients who benefit from the treatment increase the number of this new blood cell type, which fight disease.

"From a therapeutic viewpoint, our findings are really interesting and we hope that they can help find new treatment options for patients not benefiting from existing drugs, especially more chronic and progressive multiple sclerosis patients. In our model, we could activate lymphocytes by chemical stimulation and gene therapy, and we are curious whether this can be a new treatment strategy", said professor Issazadeh-Navikas.

The next phase of the team's research is to focus on developing such treatments. They have begun testing whether the FoxA1-expressing lymphocytes are able to prevent degradation of the nerve cell's myelin layer and brain degeneration in a model of progressive multiple sclerosis.

A number of other autoimmune diseases could potentially be treated by the team's research into preventing chronic inflammation, including type one diabetes, inflammatory bowel disease and rheumatoid arthritis.

During the past five years, the number of people suffering from MS has increased by ten per cent globally. It currently affects 100,000 people in the UK.

Scientists have opened up a possible new avenue for leukaemia treatment after disarming a gene responsible for tumour progression.

Researchers at the Institute for Research in Immunology and Cancer (IRIC) of the Université de Montréal targeted the Brg1 gene – a key regulator of leukaemia stem cells that are the root cause of the disease, resistance to treatment and relapse. 

The team have spent the past four years studying the gene in collaboration with another research group at Stanford University in California; their results are reported in the scientific journal, Blood.

One of the major problems faced by researchers targeting cancer stem cells is that many genes essential to their proper functioning are also essential for normal stem cells. Therapies that target them can thus also end up harming healthy cells.

"Strikingly, we showed that the Brg1 gene is dispensable for the function of normal blood stem cells, making it a promising therapeutic target in leukaemia treatment," said Pierre Thibault, principal investigator at IRIC and co-author in this study.

While promising results have been obtained on animal models and human leukaemia cells, clinical trials remain some way off. The next stage in the research will be to demonstrate the clinical relevance of the study by developing a small-molecule inhibitor to block Brg1 function in leukaemia.

Experiments are currently underway to identify drugs that can disarm the Brg1 gene and prevent leukaemia stem cells from generating malignant cells.

Cancer cells are often responsible for relapse as they are more resistant to radiotherapy and chemotherapy than the 'bulk' of the tumor. Inhibiting the division of such cells is therefore the key to obtaining irreversible impairment of tumour growth and long-term remission in patients.

Leukaemia is a cancer of the white blood cells and bone marrow. It is the twelfth most common cancer in the UK, accounting for more than two per cent of all cancers. It is the most common cancer of childhood – around a third of all cancers diagnosed in children are leukaemias.

Scientists at the University of Berkeley have discovered new evidence which shows how chronic stress can generate long-term changes in the brain and may predispose people to mental problems such as anxiety and mood disorders later in life.

It is hoped the research could help to develop treatments to reduce the risk of developing mental illness following stressful events.

People with stress-related illnesses, such as post-traumatic stress disorder (PTSD), are known to have brain abnormalities, including differences in the relative amounts of grey and white matter. 

Grey matter consists of cells called neurons, which store and process information and support called glia. White matter is composed of axons, which create a network of fibres that interconnect neurons. A fatty, myelin sheath surrounds axons and speeds the flow of electrical signals between cells.

The researchers found that chronic stress leads to the creation of more myelin-producing cells, resulting in an excess of myelin and white matter, which disrupts the balance between timing and communication in the brain.

According to Daniela Kaufer, UC Berkeley associate professor of integrative biology, people with PTSD could develop a stronger connectivity between the hippocampus and the amygdala – the seat of the brain's fight or flight response – and lower than normal connectivity between the hippocampus and prefrontal cortex, which moderates our responses.

In a study conducted on rodents, the team focussed on neural stem cells located in the hippocampus. Stem cells were previously only thought to develop into neurons or a type of glial cell called an astrocyte – but the new research found they can also develop into another type of glial cell called an oligodendrocyte, which produces the myelin that covers nerve cells.

Oligodendrocytes could play a key role in long-term and possibly permanent changes in brain chemistry which could lead to later mental problems.

As chronic stress reduces the number of stem cells that develop into neurons, this could explain how the condition affects learning and memory.

Kaufer is now conducting research into how stress in infancy affects the Brain's white matter and whether stress in early life reduces resilience later in life.

Scientists have developed a new method of identifying blood vessel plaques using nanotechnology.

The researchers, led by a team at Case Western Reserve University, designed a multifunctional nanoparticle that enables magnetic resonance imaging (MRI) to identify the plaques caused by atherosclerosis.

Currently, the method of pinpointing such plaques involves an invasive procedure, with a doctor inserting a catheter inside a blood vessel in a patient's arm, groin or neck. This emits a dye that enables X-rays to show whether the vessel is narrowing.

However, the new study used a nanoparticle built from a rod-shaped virus commonly found on tobacco, which can locate and illuminate plaque in arteries more effectively and requires just a tiny fraction of the dye.

It raises the possibility that particles could be specifically designed to distinguish vulnerable plaques from stable ones, as they are able to home in on biomarkers. Untargeted dyes are unable to do this. 

"From a chemist's point of view, it's still challenging to make nanoparticles that are not spherical, but non-spherical materials are advantageous for medical applications," said Nicole Steinmetz, assistant professor of biomedical engineering at Case Western Reserve. "Nature is way ahead of us. We're harvesting nature's methods to turn them into something useful in medicine."

In collaboration with Xin Yu, a professor of biomedical engineering, who specialises in developing MRI techniques to investigate cardiovascular diseases, Steinmetz created a device that transports and concentrates imaging agents on plaques.

Elongated nanoparticles have a higher chance of being pushed out of the central blood flow and targeting the vessel wall; they also adhere better to plaques.

The surface of the virus was modified to carry near-infrared dyes used for optical scanning and gadolinium ions (which are linked with organic molecules, to reduce toxicity of the metal). This method increases the relaxivity – contrast with healthy tissue – by more than four orders of magnitude.

As the contrast agent is delivered directly to the plaques, the scientists were able to use 400 times less of it. 

Steinmetz and Yu now want to take the research further in order to distinguish stable plaques from ones vulnerable to rupture, which require treatment. Plaques that rupture can set off the train of events which leads to a heart attack or stroke.

Researchers have discovered that a molecule which can spur the growth of muscle tissue can have the opposite effect in the endothelial cells of patients with diabetes.

The study, which was conducted at the Beth Israel Deaconess Medical Center (BIDMC), demonstrates that caution is needed when developing treatments based on a molecule known as PGC-1 alpha, as it can have different effects in different situations.

Diabetes patients are at increased risk of developing microvascular complications, which occur when the body's small blood vessels become diseased. If wounds fail to heal properly, sufferers are at risk of developing ulcers and chronic infections and, in the most serious cases, may need to undergo limb amputations.

According to the researchers, high levels of blood glucose – which occur in diabetes sufferers – stimulate production of PGC-1 alpha in the endothelial cells which line the blood vessels. This prevents the cells from functioning properly and inhibits blood vessel growth.

More than a decade's worth of studies by the laboratory has revealed the PGC-1 alpha molecule has a number of different functions. When body parts are affected by poor circulation, the molecule senses low levels of oxygen and nutrients in muscle cells and promotes angiogenesis – the growth of new blood vessels. 

A series of studies was conducted on cell cultures and mouse models, which found diabetes induces PGC-1 alpha in endothelial cells. This strongly inhibits endothelial migration and angiogenesis, leading to vascular dysfunction.

"These findings were definitely surprising, because the effects of PGC-1 alpha in endothelial cells are the opposite of its effects in muscle cells," explained senior author Zoltan Arany, an investigator at BIDMC's CardioVascular Institute and associate professor of medicine at Harvard Medical School. "In muscle cells, it's pro-metabolic and will call forth more blood vessels which come to the rescue when an injury or artery blockage leaves normal tissue starved for blood."

He said the findings show that a molecule can have dramatically different effects in different situations, so a medication which has positive effects in one cell type could have negative effects in another. Caution is therefore required when developing drugs based upon PGC-1 alpha.