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Challenges in the treatment against multiple sclerosis


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Challenges in the treatment against multiple sclerosis

  1. 1. CHALLENGES IN THE TREATMENT AGAINST MULTIPLE SCLEROSIS PGA Techniques and Applications of Molecular Biology University of Warwick Nicolas Farrands 18 July 2013
  2. 2. Outline 1 • Introduction to the Molecular Basis of MS 2 • Diagnostics Techniques 3 • Approaches in Treatment
  3. 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. 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. 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. 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. 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. 8. APPROACHES IN TREATMENT - Rebif® (Interferon-beta 1a) Copaxone® (glatiramer acetate) Gilenya® (fingolimod) Tysabri® (Natalizumab)
  9. 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. 10. Conclusion - Pathogenesis not yet fully understood - Recent research will allow more precise/rapid diagnosis - Advances in treatment thanks to biotechnology