Study Suggests FTY720 May Repair MS Damage By Direct Effect On Brain

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Main Category: Multiple Sclerosis
Also Included In: Neurology / Neuroscience;  Clinical Trials / Drug Trials
Article Date: 16 Oct 2007 - 10:00 PDT

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FTY720 (fingolimod), an oral sphingosine-1-phosphate receptor agonist being developed for multiple sclerosis (MS), acts directly on the central nervous system (CNS) to reduce disease severity in addition to peripheral effects on the immune system, according to results from a model of the disease reported at this week's European Committee for Treatment and Research in Multiple Sclerosis congress (Prague, Czech Republic).

The study in experimental autoimmune encephalomyelitis showed that administering FTY720 directly into the CNS significantly reduced disease severity. This occurred even though there was no reduction in lymphocytes in the bloodstream, indicating that the agent has a direct effect in the CNS that is independent of its effects on peripheral lymphocytes. When FTY720 is given orally, it stops lymphocytes leaving peripheral lymph nodes and infiltrating the CNS, which is another important part of its action in MS.

Anna Schubart, from Novartis Institutes for BioMedical Research, Basel, Switzerland, said: "These results suggest that the mechanism of action of FTY720 may involve CNS-mediated effects, in addition to reducing T-cell infiltration into the CNS. This raises the possibility that it might also have protective effects in progressive stages of the disease."

A further study showed that FTY720 increased the number, growth and survival of oligodendrocytes - the cells that make myelin, which insulates nerve fibres and is damaged in MS - in cell culture. This effect could potentially limit destruction of myelin and promote its repair, which could contribute to the effectiveness of FTY720 in MS. The researchers, from the Novartis Institutes for BioMedical Research, Basel, and the Brain Research Institute, Zurich, Switzerland, commented: "FTY720-mediated stimulation of S1P receptors on oligodendrocytes may help to limit demyelination and/or promote remyelination in MS."

Professor Jack Antel, from the Department of Neurology and Neurosurgery at McGill University, Montreal, Canada, said: "FTY720 crosses the blood-brain barrier and the drug's target - S1P receptors - are present on brain cells, including oligodendrocytes, as shown in animal cell studies." He added: "We are able to confirm that FTY720 directly modulates the S1P receptors on human oligodendrocyte progenitor cells."

Results from a phase II study in 281 patients with relapsing MS (the commonest type) showed that once-daily, oral FTY720, reduced relapse rates by more than 50% after six months, compared to placebo. It also reduced magnetic resonance imaging (MRI) measures of inflammation, with around 80% of patients free of active brain lesions. In patients continuously treated with FTY720 for up to two years, up to 77% remained relapse-free and more than 80% were free of active brain lesions at two years. FTY720 is being further investigated in the largest phase III clinical trial programme yet to be carried out in MS.

-- European Committee for Treatment and Research in Multiple Sclerosis congress
-- Novartis Institutes for BioMedical Research

Written by: Susan Mayor PhD, freelance medical journalist, London, UK
mayor at dircon.co.uk
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