1. By Matthew Sampson

2. Overview What is it? Previous Treatments Monoclonal Antibodies Chimeric Molecules Oral Therapies Hematopoietic Stem Cells Future

3. What Is Multiple Sclerosis? Multiple sclerosis is a disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms. The symptoms of MS can affect all parts of the body. The cause of MS is still unknown, but it most likely is some combination of genetic, environmental, and infectious factors.

4. Previous Treatments Over the last 2 decades the treatments for Multiple Sclerosis have evolved rapidly The introduction of interferon-β, and glatiramer acetate has demonstrated efficiency in reducing relapse rates and MRI lesion burden, as well as in delaying the accumulation of disability. Depending upon the condition and symptoms of the patients MS will dictate what treatment they shall receive.

5. Monoclonal Antibodies Monoclonal antibodies are monospecific antibodies that are the same because they are made by one type of immune cell which are all clones of a unique parent cell. Some such monoclonal antibodies that they have tried are Natalizumab, rituximab, Alemtuzumab, and Daclizumab The greatest success was seen using Alemtuzumab. It reduced the relapse rate by 74% and reduced the risk of sustained disability by 71%. Alemtuzumab also demonstrated superiority on MRI, with a greater reduction in T2 lesion load and less atrophy on T1 images.

6. Chimeric Molecules A chimeric molecules is a molecule containing sequences derived from two different genes; specifically, from two different species. Abatacept is a chimeric molecule composed of a human CD152 molecule and an IgG tail. The CD152 domain binds to CD80 and CD86 on antigen- presenting cells, blocking their ability to bind to CD28 on T-cells, which would otherwise lead to T-cell activation. They have been unable to properly test this drug due to an imbalance in the test group.

7. Oral Therapies Oral therapy would be the change from self-injection prescribed therapy to an oral medication. Oral fingolimod is currently in phase III evaluation in relapsing–remitting and progressive forms of MS. The relapse rate showed a relative reduction of 53% in the 5.0-mg group and 55% in the 1.25-mg group. However, there were no significant differences between placebo and treatment groups in EDSS score at 12 months. A later publication of 24-month data, showed continued benefit to patients in terms of less MRI activity and lower relapse rate and, additionally, there were no further serious adverse events in the safety evaluation.

8. Hematopoietic Stem Cells Hematopoietic stem cells are multipotent stem cells that give rise to all the blood cell, and lymphoid lineages. The integration of hematopoietic stem cell transplantation into medical regimens for autoimmune disease has been investigated as a means for complete reversal of the autoimmune response. Confirmed progression-free survival was seen in 74% at 3 years, and post-transplant gadolinium-enhanced lesions on MRI occurred in only 8% of cases. However, this study showed relatively significant toxicity, with 15% of patients having serious infections, allergic events, or severe related bone pain.

9. Future… Proteomic techniques also show promise in the search for novel therapeutic targets. From this analysis, tissue factor and protein C inhibitors appear to be the most promising targets. Tissue factor may exert an effect on MS lesions via its activation of thrombin, while PCI inhibits the protein C pathway. Another novel target under investigation is the voltage-gated potassium channel Kv1.3, which is specifically regulated on effector T-cells. Much research has to be done before this approach can be tested in human subjects.

10. Future Cont. There are also therapies that may prevent the degeneration of axons and/or promote remyelination. The myelin-associated glycoprotein (MAG) is a strong candidate for interventions that may lead to prevention of axonal degeneration One potential target for promotion of remyelination is the LINGO-1 protein. It has been recently discovered that this molecule is a potent inhibitor of oligodendrocyte progenitor cells and thus an inhibitor of myelination.

11. Work Cited Harrison, Daniel M., and Peter A. Calabresi. "Promising Treatments of Tomorrow for Multiple Sclerosis." Annals of Indian Academy of Neurology 12.4 (2009): 283-290. Web. 27 Mar 2010. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC28249 56/?tool=pubmed(journal) http://en.wikipedia.org/wiki/Monoclonal_antibodies http://en.wikipedia.org/wiki/Multiple_sclerosis http://en.wikipedia.org/wiki/Hematopoietic_stem_cel l