Treating multiple sclerosis
Researchers at the Dunn School of Pathology at the University of Oxford have played a major role in the development of an effective and innovative treatment for the chronic debilitating disease multiple sclerosis.
Multiple sclerosis (MS) affects 2.5 million people worldwide and approximately 100,000 people between the ages of 20-40 years in the UK. In this chronic debilitating condition the patient’s immune system attacks their own nerve cells resulting in symptoms including numbness, tingling, blindness and even paralysis. The majority (65%) of patients relapse into a secondary progressive phase, which is punctuated with episodes of disease with incomplete recovery. The prognosis is difficult to predict but the life expectancy for MS sufferers is generally 5-10 years lower than expected. There is no cure and conventional treatments such as interferon beta require frequent administration and are only moderately effective.
Ground breaking research by Professors Herman Waldmann, Geoff Hale and colleagues from the Dunn School of Pathology has shown that alemtuzumab, an antibody directed against the lymphocyte surface maker CD52, offers a potential cure for many patients with MS. Working together with clinicians from the University of Cambridge, the team published the results of their game changing clinical study in 1999. This showed that a short course of alemtuzumab induced selective lymphocyte depletion, reduced inflammatory mediators that contribute to the disease and reduced inflammation of the nervous system. This study highlighted the link between inflammation and demyelination of nerves and the effect of inflammatory mediators on the exposed nerve fibres. The conclusion was that treatment to reduce inflammation should begin as soon as possible.
The team followed this up with a study using short term (up to 8 days) pulsed alemtuzumab treatment in a larger group of patients. This confirmed the beneficial reduction in the inflammatory response and reduced number of relapses. Patients treated with alemtuzumab experienced reduced disability even after three years. A parallel study showed there was a differential recovery of lymphocytes, effectively ‘resetting’ the immune system.
Traditional MS treatments are either poorly efficacious, or compromise the whole immune system risking the development of cancers and infections. However, short-term treatment with alemtuzumab results in long-term benefit for the patient with less risk of infection.
Alemtuzumab has been developed by Genzyme Corporation under the name of Lemtrada. In a phase III clinical trial, involving 840 patients, Lemtrada achieved reduced relapse and disability rates compared to beta interferon. Remarkably 65% of patients remained relapse free after two years.
As a result of these exceptional results the drug has received regulatory approval worldwide. Its potential income from Lemtrada has been estimated to be at least $1bn annually.