SCIENTISTS DISCOVER HOW TO SWITCH OFF AUTOIMMUNE DISEASES

Scientists have made an important breakthrough in the fight against debilitating autoimmune diseases such as multiple sclerosis by revealing how to stop cells attacking healthy body tissue.

Rather than the body's immune system destroying its own tissue by mistake, researchers at the University of Bristol have discovered how cells convert from being aggressive to actually protecting against disease.

The study, funded by the Wellcome Trust, is published in Nature Communications.

It's hoped this latest insight will lead to the widespread use of antigen-specific immunotherapy as a treatment for many autoimmune disorders, including multiple sclerosis (MS), type 1 diabetes, Graves' disease and systemic lupus erythematosus (SLE).

MS alone affects around 100,000 people in the UK and 2.5 million people worldwide.

Scientists were able to selectively target the cells that cause autoimmune disease by dampening down their aggression against the body's own tissues while converting them into cells capable of protecting against disease.

This type of conversion has been previously applied to allergies, known as 'allergic desensitisation', but its application to autoimmune diseases has only been appreciated recently.

The Bristol group has now revealed how the administration of fragments of the proteins that are normally the target for attack leads to correction of the autoimmune response.

Most importantly, their work reveals that effective treatment is achieved by gradually increasing the dose of antigenic fragment injected.

In order to figure out how this type of immunotherapy works, the scientists delved inside the immune cells themselves to see which genes and proteins were turned on or off by the treatment.

They found changes in gene expression that help explain how effective treatment leads to conversion of aggressor into protector cells. The outcome is to reinstate self-tolerance whereby an individual's immune system ignores its own tissues while remaining fully armed to protect against infection.

By specifically targeting the cells at fault, this immunotherapeutic approach avoids the need for the immune suppressive drugs associated with unacceptable side effects such as infections, development of tumours and disruption of natural regulatory mechanisms.

Professor David Wraith, who led the research, said: "Insight into the molecular basis of antigen-specific immunotherapy opens up exciting new opportunities to enhance the selectivity of the approach while providing valuable markers with which to measure effective treatment. These findings have important implications for the many patients suffering from autoimmune conditions that are currently difficult to treat."

This treatment approach, which could improve the lives of millions of people worldwide, is currently undergoing clinical development through biotechnology company Apitope, a spin-out from the University of Bristol.

SCIENTISTS DISCOVER NEW CAUSE OF GLAUCOMA

Scientists have revealed that they have discovered a novel cause of glaucoma in an animal model and are developing an eye drop aimed at curing the disease.

The new study for the first time identifies the molecular building blocks needed to make the 'drainage' vessels, providing the necessary chemical tools to repair the eye's plumbing and restore normal drainage. Up until now, the molecular basis of the disease caused by an absent or defective canal was unknown.

Senior study author and Northwestern Medicine nephrologist Susan Quaggin said that this is a big step forward in understanding the cause of the disease that steals the eyesight from 60 million people worldwide, which gives them a foothold to develop new treatments.

The findings are based on a new mouse model of glaucoma developed by the researchers is one of the first animal models of the disease and researchers expect the animal findings to be relevant in human glaucoma.

The researchers have developed a highly potent peptide nanostructure that has the capacity to interact with many receptors at the same time, which will amplify the required signaling pathway for an effective therapy. The nanostructure is also being designed to have the necessary half-life to optimize efficacy.

The study was The Journal of Clinical Investigation.

SIGNATURE OF AGING IN BRAIN SCIENTISTS SUGGEST THAT THE BRAINS IMMUNOLOGICAL AGE IS WHAT COUNTS

How the brain ages is still largely an open question -- in part because this organ is mostly insulated from direct contact with other systems in the body, including the blood and immune systems. In research that was recently published in Science, Weizmann Institute researchers Prof. Michal Schwartz of the Neurobiology Department and Dr. Ido Amit of Immunology Department found evidence of a unique "signature" that may be the "missing link" between cognitive decline and aging. The scientists believe that this discovery may lead, in the future, to treatments that can slow or reverse cognitive decline in older people

Until a decade ago, scientific dogma held that the blood-brain barrier prevents the blood-borne immune cells from attacking and destroying brain tissue. Yet in a long series of studies, Schwartz's group had shown that the immune system actually plays an important role both in healing the brain after injury and in maintaining the brain's normal functioning. They have found that this brain-immune interaction occurs across a barrier that is actually a unique interface within the brain's territory.

This interface, known as the choroid plexus, is found in each of the brain's four ventricles, and it separates the blood from the cerebrospinal fluid. Schwartz: "The choroid plexus acts as a 'remote control' for the immune system to affect brain activity. Biochemical 'danger' signals released from the brain are sensed through this interface; in turn, blood-borne immune cells assist by communicating with the choroid plexus.This cross-talk is important for preserving cognitive abilities and promoting the generation of new brain cells."

This finding led Schwartz and her group to suggest that cognitive decline over the years may be connected not only to one's "chronological age" but also to one's "immunological age," that is, changes in immune function over time might contribute to changes in brain function -- not necessarily in step with the count of one's years.

To test this theory, Schwartz and research students Kuti Baruch and Aleksandra Deczkowska teamed up with Amit and his research group in the Immunology Department. The researchers used next-generation sequencing technology to map changes in gene expression in 11 different organs, including the choroid plexus, in both young and aged mice, to identify and compare pathways involved in the aging process.

That is how they identified a strikingly unique "signature of aging" that exists solely in the choroid plexus -- not in the other organs. They discovered that one of the main elements of this signature was interferon beta -- a protein that the body normally produces to fight viral infection. This protein appears to have a negative effect on the brain: When the researchers injected an antibody that blocks interferon beta activity into the cerebrospinal fluid of the older mice, their cognitive abilities were restored, as was their ability to form new brain cells. The scientists were also able to identify this unique signature in elderly human brains. The scientists hope that this finding may, in the future, help prevent or reverse cognitive decline in old age, by finding ways to rejuvenate the "immunological age" of the brain.