The inflamed brain

Leading research into novel and effective treatments for multiple sclerosis

Cambridge has been leading research into monoclonal antibodies to identify effective treatments for multiple sclerosis

What can be done when the body launches an immune attack against its own tissue? The autoimmune disease multiple sclerosis is the most common disabling neurological condition to affect young adults, with over 85,000 people affected in the UK, over 250,000 in the USA, and about 2.5 million people worldwide. Multiple sclerosis occurs when the protective sheath around nerve fibres in the central nervous system, called myelin, is damaged. Depending on the part affected, this leads to disturbances of vision, movement, sensation and basic bodily functions such as bladder control.

Researchers at Cambridge have pioneered the use of monoclonal antibodies to identify an effective treatment for multiple sclerosis. Antibodies provide a natural defence mechanism against invading foreign substances. In the 1980s, Nobel Prizewinning research at the Laboratory of Molecular Biology in Cambridge showed that monoclonal antibodies, designed to target specific antigens, could be produced in almost unlimited quantities. Researchers from the Department of Pathology seized on this discovery and went a step further to create ‘humanised’ monoclonal antibodies for use as medicines. The first, Campath-1H, went on to be developed as a treatment for chronic lymphatic leukaemia.

Scientists at the Cambridge Centre for Brain Repair and the Department of Clinical Neurosciences have recently begun a Medical Research Council funded trial into the effects of autologous adult stem cells on patients with progressive multiple sclerosis

A team at the Department of Clinical Neurosciences entered this area of research in 1991, and has since continued to study Campath-1H by painstakingly investigating its effects in multiple sclerosis. Building up from single case studies in individual patients, a large Phase II international multi-centre trial was completed in 2007. Interim results at the end of two years were announced in September 2006, and confirmed what the Cambridge-based investigators had recognised for several years. Given early in the course of relapsing-remitting multiple sclerosis, Campath-1H causes a significant reduction in the occurrence of new episodes – by more than 90% in this trial. Campath-1H appears to stop the development of multiple sclerosis in its tracks, by inhibiting new tissue injury in the central nervous system. Remarkably, these long-term effects are achieved following only one week of exposure to Campath-1H every 12-18 months. But as with all potential new advances, treatment is not uncomplicated. Surprisingly, in this context, although the autoimmune process of multiple sclerosis seems to be suppressed, a range of other conditions – also autoimmune in their mechanisms – emerge as a complication of treatment; nevertheless the patients still consider the benefits of Campath-1H to outweigh the risks of these treatable disorders. Phase III studies of alemtuzumab (as Campath-1H is now known) are due to be launched in 2007, highlighting how coordinated and interactive research within a university environment can lead to the development of effective clinical treatments.

Cambridge researchers have simultaneously been exploring other avenues of potential therapy for patients with multiple sclerosis, by developing techniques that may enable the brain to repair damaged myelin and nerve cells itself. Using adult stem cells, which are derived from a patient’s own tissues – not necessarily of brain origin – scientists at the Cambridge Centre for Brain Repair (Department of Clinical Neurosciences) have recently begun a MRC funded trial into the effects of autologous adult bone marrow stem cells in patients with multiple sclerosis.