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mmcc53
10-06-2006, 07:36 PM
Since we are working on getting the research articles back, here's another:

May 06, '06: Newly Recognized Immune Cells May Lead to New Therapies
Category: General
Posted by: stuart
Research Highlights Winter/Spring 2006
http://www.nationalmssociety.org/Highlights-ImmuneCells.asp


Newly Recognized Immune Cells May Lead to New Therapies



There?s a new T cell in town, and unlike the white blood cells that drive the immune attack on the brain and spinal cord in multiple sclerosis, these T cells may actually inhibit the immune response. ?T regs? are regulatory T cells that have emerged over the past few years as major players in inhibiting autoimmune disease in rodent models and humans. MS researchers are exploring what happens to T regs in people with MS, and whether therapeutic strategies can take advantage of their regulatory capabilities.





David Hafler, MD (Harvard?s Brigham & Women?s Hospital, Boston) and colleagues sought to determine whether T reg cells were altered in people with MS, with funding from a National MS Society research grant. They examined blood samples from 15 untreated people with relapsing-remitting MS and compared results with samples from 21 people without MS. Although T reg cells existed in the same frequency in people with MS, the function of these cells was significantly impaired (Journal of Experimental Medicine 2004:199;971-979).



Stephen Miller, PhD (Northwestern University Medical School, Chicago, IL) and colleagues supplemented the number of T reg cells in mice with the MS-like disease, EAE (Journal of Immunology 2002 Nov 1;169(9):4712-6). This increased the mice?s resistance to disease. Interestingly, the number of disease-causing T cells did not decrease, but clinical symptoms did, indicating that T reg cells do not prevent activation of T cells, but rather influence trafficking of activated cells.



Miller is exploring these results further with a research grant from the Society. His team recently administered molecules that inhibit CD3 (a protein on the surface of inflammatory T cells that helps them to function) to mice with EAE. T reg cells were almost doubled with this anti-CD3 treatment. Treatment significantly prevented disease progression when administered after disease initiation, but if administered before, did not influence disease course (Journal of Immunology 2005 Apr 15;174(8):4525-34). These results suggest that anti-CD3 is an effective treatment for established EAE, and warrants further study to determine its feasibility for MS.



Arthur Vandenbark, PhD (VA Medical Center, Portland) and colleagues have studied FOXP3, a newly identified gene that has been found to affect T reg cell activity. His team looked at FOXP3 levels in blood samples from five people with MS and five people without MS. FOXP3 levels were decreased in people with MS, a finding that correlated with reduced immunosuppression (Journal of Neuroscience Research 2005 Jul 1;81(1):45-52).



One treatment under study in people with MS may help resolve T reg deficiencies in this population. Vandenbark and colleagues recently reported on an ongoing clinical trial of NeuroVaxTM (Immune Response Corporation) in people with relapsing and progressive MS. NeuroVax is a vaccine made of protein fragments from a docking site on the surface of T cells. By examining blood samples taken from six people before and after three monthly injections, investigators found that FOXP3 levels were increased to a level equal to controls without MS, indicating that this treatment might succeed in replenishing T reg cells in people with MS (21st Congress of the European Committee for Treatment and Research in Multiple Sclerosis, 2005). Further results from all subjects are necessary to confirm the findings.



These data present novel opportunities to develop strategies to increase T reg cells, possibly dampening the immune attack that occurs in MS.

*Joy*
10-11-2006, 08:28 AM
Does anyone have additional information about NeuroVax? Mark?

xo++
10-11-2006, 08:54 AM
Hi Joy,

Timely posting by Marcy since yesterday the company (Immune Response Corporation) announced (http://www.imnr.com/news/2006/2006OCT10.htm) the launching of a phase II double-blinded placebo controlled trial, enrolling 200 RRMS patients. The trial will last 48 weeks.

Dr. Dennis Bourdette at Oregon Health Sciences is one of the lead investigators, and he's really at the forefront of MS therapeutic research. (He's also taken the lead investigating alpha lipoic acid as a therapy in MS.)

Results of altered peptide therapies have been somewhat disappointing in the past, with allergic reactions being a problem (e.g. see here (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=11017151&query_hl=5&itool=pubmed_docsum) for an altered peptide MS trial suspended because of allergic reactions, and here (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=11017150&query_hl=5&itool=pubmed_docsum) for another unsuccessful trial).

Here (http://www.imnr.com/news/2006/2006APR06.htm) is the company's press release which discusses the effects of the vaccine on FoxP3.

Mark

*Joy*
10-11-2006, 10:27 AM
Thank you, Mark. :)

It doesn't seem very promising for us.

It says in the article that people with MS have diminished levels of FOXP3 (a genetic marker). Are they saying that there may be a genetic link to MS?