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
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
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
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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