Challenges in the treatment against multiple sclerosis
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CHALLENGES IN THE TREATMENT AGAINST MULTIPLE SCLEROSIS PGA Techniques and Applications of Molecular Biology University of Warwick Nicolas Farrands [email protected] 18 July 2013
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Transcript of Challenges in the treatment against multiple sclerosis
CHALLENGES IN THE TREATMENT AGAINST MULTIPLE SCLEROSIS
PGA Techniques and Applications of Molecular BiologyUniversity of Warwick
Nicolas [email protected]
18 July 2013
• Introduction to the Molecular Basis of MS1
• Diagnostics Techniques2
• Approaches in Treatment3
Outline
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
Molecular Basis of MSA 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…
- 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
Diagnostics Methods
An on-going studyHLA-DR Microarray
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.
HLA-DRB5 highly expressed in MS patients
Oligoclonal Bands Analysis
Gel isoelectric focusing (IEF) of cerebrospinal fluid
Imaging Capillary IEF-Western Blot
- Suggests intrathecal synthesis of IgG- 95% accurate when combined with
imaging diagnostic- Very invasive (lumbar puncture)
APPROACHES IN TREATMENT
- Rebif® (Interferon-beta 1a)- Copaxone® (glatiramer acetate)- Gilenya® (fingolimod)- Tysabri® (Natalizumab)
Therapeutic Monoclonal AntibodiesRecombinant DNA TechnologyAlemtuzumab (Campath-1H®) Phase IIIMonoclonal 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
Conclusion
- Pathogenesis not yet fully understood- Recent research will allow more precise/rapid diagnosis- Advances in treatment thanks to biotechnology
THANK YOU.
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