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Challenges in the treatment against multiple sclerosis
- 1. CHALLENGES IN THE TREATMENT AGAINST MULTIPLE SCLEROSIS PGA Techniques and Applications of Molecular Biology University of Warwick Nicolas Farrands nic.farrands@gmail.com 18 July 2013
- 2. Outline 1 • Introduction to the Molecular Basis of MS 2 • Diagnostics Techniques 3 • Approaches in Treatment
- 3. Multiple Sclerosis - Demyelinating disease of auto inflammatory origin Pathogenesis not yet fully understood Thought to be caused by environmental factors and genetics Affects both men and women in a variety of physical, mental and psychiatric symptoms
- 4. Molecular Basis of MS A variety of genes are thought to be involved in the development of Multiple Sclerosis. - Specific genes in the Human Leukocyte Antigen (HLA) system on Chromosome 6 are affected - The Epstein-Barr Virus also found to increase risk - Other factors such as infantile viral illnesses (MMR), stress, smoking…
- 5. Diagnostics Methods - Magnetic resonance imaging: demyelination zones Genotyping by PCR Isoelectric focusing analysis of the CSF CD52 antigen (12 AA peptide) levels in serum by ELISA Biomarker identification Association mapping of HLA-DRB1 genetic mutations
- 6. HLA-DR Microarray An on-going study HLA-DRB5 highly expressed in MS patients J Neuroimmunol. 2013 Apr 15;257(1-2):90-6. doi: 10.1016/j.jneuroim.2013.02.004. Epub 2013 Mar 9. Genome wide differences of gene expression associated with HLA-DRB1 genotype in multiple sclerosis: a pilot study. Apperson ML, Tian Y, Stamova B, Ander BP, Jickling GC, Agius MA, Sharp FR.
- 7. Oligoclonal Bands Analysis Gel isoelectric focusing (IEF) of cerebrospinal fluid - Suggests intrathecal synthesis of IgG - 95% accurate when combined with imaging diagnostic - Very invasive (lumbar puncture) Imaging Capillary IEF-Western Blot
- 8. APPROACHES IN TREATMENT - Rebif® (Interferon-beta 1a) Copaxone® (glatiramer acetate) Gilenya® (fingolimod) Tysabri® (Natalizumab)
- 9. Therapeutic Monoclonal Antibodies Recombinant DNA Technology Alemtuzumab (Campath-1H®) Phase III Monoclonal antibody raised against CD52 - VH and VL sequences obtained from libraries and vectors are created - Both vectors are fused together - Fusion results in production of scFv - Conversion to IgG in mammalian cells
- 10. Conclusion - Pathogenesis not yet fully understood - Recent research will allow more precise/rapid diagnosis - Advances in treatment thanks to biotechnology
Hinweis der Redaktion
- This group of genes resides on chromosome 6, and encodes cell-surface antigen-presenting proteins and has many other functions.HLAs corresponding to MHC class II (DP, DM, DOA, DOB, DQ, and DR) present antigens from outside of the cell to T-lymphocytes. These particular antigens stimulate the multiplication of T-helper cells, which in turn stimulate antibody-producing B-cells to produce antibodies to that specific antigen. The major HLA antigens are essential elements for immune function.
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