Previous work has shown that blood vessels at the sites of inflammation express markers of inflammation that circulating immune cells in the blood recognise and use to enter inflamed tissue. We are using the latest gene chip technology to work out which genes are turned on or off in brain blood vessels purified from active lesions in MS tissue. This will increase our understanding of how the demyelinating inflammatory cells gain access to the brain. Stopping this process is already the basis of effective treatment (e.g. natalizumab TYSABRI) but we do not know why the blood vessels become inflamed in the first place. One theory is that virus infection promotes the inflammation and we have been collaborating with scientists in the USA who hunt for viruses using virus gene chips. We also think that the degeneration of the brain accompanying progressive MS might be caused by a general failure of brain blood vessel function. The brain cannot tolerate even the briefest interruption to its blood supply (unlike the heart, kidney or liver) and our first gene profiles of blood vessels purified from parts of the brain not involved in the MS lesions are very abnormal with the genes of several important transporters of nutrients and hormones to the brain being reduced. Once this work has been confirmed, we will try and prove that these changes have severe consequences for brain function in animal models. We hope that this work will contribute to our understanding of progressive MS for which there is no effective treatment at the moment.
This work uses post mortem MS brain tissue, kindly supplied by the UK MS Tissue Bank. We hope to use the high quality MS brain tissue being deposited in the Australian MS Research Australia Brain Bank, when it becomes available.
While we don’t know the cause of MS, there is some evidence that infection may play a part in the process that leads to neural damage. Prof Simon Hawke is scouring the thin layer of ‘endothelial cells’ that line the inside of blood vessels for signs of lurking viruses that can trigger MS.
Prof Hawke explains, “MS lesions congregate around one or more blood vessels in the brain. Virus infection in and around the blood vessels might be responsible for interfering with the body’s rigorous security barrier which protects the brain from attacking agents in the blood. Normal functioning of the blood brain barrier is essential for maintaining healthy brain function.”
“Until recently, it has not been possible to comprehensively survey viruses. This cutting edge technology is still not generally available and in collaboration with Dr DeRisi of the University of California (USA) who developed the ‘VIROCHIP©’, Prof Hawke will scan for all known viruses that might be hiding in MS tissue.
The project utilises human tissue from the UK MS Tissue Bank. Prof Hawke highlights “Using human brain tissue is imperative if we’re to understand the disease sooner rather than later. The MS Research Australia Brain Bank is a growing source of human tissue set aside specifically for MS research and gives people with MS the opportunity to play their part in giving the next generation freedom from MS.”
Prof Hawke is hopeful that, “This data will allow us not only to reach a much better understanding of disease pathogenesis, but also to develop new strategies for the therapy of progressive disease.”
Professor Simon Hawke and his colleagues have been investigating the genetic regulation changes in MS brain blood vessels using powerful DNA technology. This research suggests that blood vessels are generally inflamed, even in areas of the brain that look normal and even in people who have had the disease for many years.
This supports the idea that MS to some extent affects the whole brain and we now think that the widespread blood vessel inflammation might interfere with the supply of brain nutrients and with the removal of toxic substances from the brain.
Given the extremely rapid and serious consequences of interrupting the brain’s blood supply (resulting in a stroke) and the unique characteristics of the blood brain barrier in controlling the transport of its energy and other requirements, it may be that problems with transporter proteins may lead to a lack of, or toxic levels of, important brain chemicals in MS that might affect general brain function; perhaps even explaining the progressive loss of brain tissue (atrophy) and general symptoms such as fatigue, depression and cognitive problems that are a feature of the disease even in its early stages.
Updated: 06 January, 2008