Multiple sclerosis (MS) is an auto-immune disease in which the myelin sheaths surrounding nerve fibres are destroyed. The disease affects millions of people worldwide and can lead to loss of sight and mobility as well as depression, fatigue and problems with cognition. There is currently no cure, and few truly effective treatments.
A study published in the New England Journal of Medicine describes the results of a randomized, blinded, phase II clinical trial examining the effects of alemtuzumab in patients with previously untreated, early, relapsing-remitting multiple sclerosis. Alemtuzumab is a humanized monoclonal antibody that targets the CD52 receptor on lymphocytes and monocytes and is prescribed for the treatment of chronic lymphocytic leukemia and T-cell lymphoma. Patients with scores of 3.0 or less on the Expanded Disability Status Scale and disease duration of 3 years or less were assigned to receive either subcutaneous interferon β-1a, (44 µg) three times per week, or annual intravenous cycles of alemtuzumab (either 12 mg or 24 mg per day) for 36 months. Interferon β-1a is one of the most effective licensed therapies for similar cases of MS. Alemtuzumab therapy was suspended in September 2005 after immune thrombocytopenic purpura developed in three patients, one of whom died. Treatment with interferon β-1a continued for the full duration of the study.
Alemtuzumab treatment was found to significantly reduce the rate of sustained accumulation of disability by 71% and the annualized rate of relapse by 74% compared with interferon β-1a treatment. Importantly, the mean disability score on a 10-point scale improved by 0.39 point in the alemtuzumab group and worsened by 0.38 point in the interferon β-1a group. The lesion burden was also reduced in the alemtuzumab group compared with the interferon β-1a group and, from month 12 to month 36, brain volume increased in the alemtuzumab group but decreased in the interferon β-1a group.
The incidence of side effects was somewhat higher in the alemtuzumab group compared with the interferon β-1a group. Adverse events included thyroid disorders (23% vs 3%), immune thrombocytopenic purpura (3% vs 1%) and infections (66% vs 47%). There were no significant differences in outcomes between the 12-mg dose and the 24-mg dose of alemtuzumab.
Multiple sclerosis (MS) is a disorder of the central nervous system with initial inflammation of the protective myelin sheath encasing nerve fibres. Symptoms vary widely and often occur initially as discrete episodes interspersed with relatively symptom-free periods (relapsing MS).
A drug currently being tested for its effectiveness in treating relapsing forms of MS is now to be tested to see whether it can prevent the disease from developing. The drug, cladribine, will be given orally to patients who have a first clinical event suggestive of MS. Patients will be treated for two years, or up to the time when they experience a second attack leading to a definite clinical diagnosis of MS. Treatment will be given in two or four cycles in the first year, with a single daily dose of cladribine tablets being given on four to five consecutive days in each cycle. This means that patients in the study will take cladribine for only 8 – 20 days in the first year. In the second year, two treatment cycles will be given to all patients.
Cladribine is also used as an intravenous infusion to treat hairy cell leukemia, chronic lymphocytic leukemia, and non-Hodgkin’s lymphomas.
A drug that is being developed to treat multiple sclerosis (MS) by damping down the immune system may also have the potential to treat viral infections. A study published in the journal, Nature, showed that mice treated with the drug FTY-720 (fingolimod) were able to clear a viral meningitis infection that persisted in untreated mice.
It is, at first sight, surprising that a drug developed to suppress the immune response in MS patients can help to fight a viral infection.
FTY720-P is an agonist of the sphingosine-1-phosphate receptor and causes lymphopenia by preventing egress of lymphocytes from the lymph nodes. The new finding builds on the observation that more easily cleared strains of the virus also cause lymphocytes to become sequestered in lymph nodes. The reason why trapping circulating lymphocytes allows a more robust response to infection is not clear, but may be linked to the fact the lymph nodes are where the immune response is primed. Clearance of the virus does not occur when CD4 T cells are absent at the time of treatment, indicating that the drug is not exerting direct antiviral effects. Some viruses, including HIV, replicate at high levels in lymph nodes and the team plan to test the effect of FTY720 on infection with other viruses.
FTY720 is currently in Phase III clinical trials to test its safety and efficacy as a disease modifying therapy for relapsing-remitting MS.