Promising Emerging Therapies for Multiple Sclerosis
Section snippets
Potential targets for treating multiple sclerosis
Targets for treating MS include immune dysfunction (anti–T- and anti–B-cell therapies), immune regulation (enhancing T-regulatory function), reducing permeability of BBB, preventing transmigration of cells across the BBB (antiadhesion molecule therapies), targeting key mediators of the inflammatory cascade (anticytokine therapies), putative autoantigens (immune tolerance), reducing demyelination, preventing neuroaxonal loss (neuroprotection), promoting remyelination, and augmenting regenerative
Anti-CD52 (Alemtuzumab [Campath-1H])
Alemtuzumab (Genzyme and Bayer Schering) is currently in late phase III development. Alemtuzumab is a humanized IgG1 mAb that binds to CD52 on leukocytes. It rapidly depletes CD52-bearing leukocytes, which include T cells, B cells, NK cells, monocytes and macrophages, and some granulocytes.20 Whether or not it functions by depleting autoreactive cells directly involved in the autoaggressive cascade is a moot point. Other actions of alemtuzumab include stabilization the BBB and possible
Oral agents
Current first-line DMTs are administered as subcutaneous or intramuscular (IM) injections and are associated with frequent side effects, including injection site reactions, flu-like symptoms, and lipoatrophy, although the more effective natalizumab and the mAbs (discussed previously) require regular parenteral administration and come with potential life-threatening side effects and/or undefined long-term risks. Therefore, the holy grail of MS has been to develop oral agents that are at least as
Summary
Not all patients respond to interferon beta and glatiramer acetate treatment. For suboptimal or nonresponders, current options include switching between classes or escalating therapy to natalizumab or mitoxantrone. The recent licensing of cladribine and fingolimod in some countries expands the options of treatment for patients who are treatment-naïve and those who are failing parenteral therapies because of lack of efficacy, poor tolerance, or unacceptable risks (eg, PML on natalizumab). The
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Disclosures: Professor Giovannoni has received consulting fees from Bayer Schering Healthcare, Biogen-Idec, FivePrime Therapeutics, Genzyme, GlaxoSmithKline, GW Pharma, Ironwood Pharmaceuticals, Merck-Serono, Novartis, Protein Discovery Laboratories, Roche, Teva-Aventis, Vertex Pharmaceuticals, and UCB Pharma; lecture fees from Bayer Schering Healthcare, Biogen-Idec, Pfizer, Teva-Aventis, and Vertex Pharmaceuticals; and grant support from Bayer Schering Healthcare, Biogen-Idec, GW Pharma, Merck-Serono, Merz, Novartis, Teva-Aventis, and UCB Pharma.