Transcript Promising Future Treatments for Multiple Sclerosis

By Matthew Sampson
Overview
 What is it?
 Previous Treatments
 Monoclonal Antibodies
 Chimeric Molecules
 Oral Therapies
 Hematopoietic Stem Cells
 Future
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.
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.
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.
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 antigenpresenting 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.
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.
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.
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.
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.
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
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