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Crohn's Disease Forum » Books, Multimedia, Research & News » Compugen announces initial validation results for two novel immunomodulatory proteins


04-24-2012, 11:35 AM   #1
Igor_Passau
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Compugen announces initial validation results for two novel immunomodulatory proteins

Furthermore, CGEN-15001T, the membrane protein that CGEN-15001 is based on, was recently shown to be expressed in samples from the gastrointestinal tracts of patients diagnosed with Crohn's disease and ulcerative colitis, the two major types of inflammatory bowel disease. CGEN-15001T was shown to be specifically over expressed on both the epithelium and immune cells in diseased tissues, compared with the respective normal tissues. These findings further support CGEN-15001's immunomodulatory role and indicate CGEN-15001ís additional potential utility in the treatment of these inflammatory bowel diseases, which also represents a major unmet medical need for new, more effective therapies.
http://www.freshnews.com/news/640888...proteins-and-f
04-24-2012, 12:12 PM   #2
SarahD
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I notice these findings come from a mouse model, I wonder how or if they translate to humans? Perhaps Judith can help explain things help here.
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Symptoms from the age of 12. Mis-diagnosed with UC at the age of 13, and later diagnosed with Crohn's in January 2012 at 24 years old. Disease mainly in terminal ileum.


Current meds:
Azathioprine, Allopurinol, Calcichew D3-Forte, Fortijuice, Alendronic acid, Ranitidine

Previous meds:
Augmentin, Doxycycline, Lansoprazole, Asacol, Pentasa, Prednisolone, Entocort, Cipro, Flagyl, Elemental Extra 028
04-25-2012, 02:22 AM   #3
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I notice these findings come from a mouse model, I wonder how or if they translate to humans? Perhaps Judith can help explain things help here.
Hi SarahD,
With regards to Compugen's mouse models of autoimmune disease, they are pretty standard models used in very early studies for new therapeutic drugs.

They used two different autoimmune disease models:
First, was a study of the drug's effect on an experimentally generated model of RA (Rheumatoid Arthritis). RA is an autoimmune disease in which the immune system attacks joints and can lead to painful arthritis and severe damage of joints. The model they used for RA, called the CIA model (CIA= Collagen - Induced Arthritis) basically consists of mice being "vaccinated" against type II Collagen. The Collagen vaccine results in an autoimmune response to Collagen, resulting in RA-like symptoms in the mouse model.

The second model Compugen used was a mouse model for MS (Multiple Sclerosis). MS is an autoimmune disease in which the body mounts an immune response against myelin found in many types of nerve cells. The MS model, or Experimental autoimmune encephalomyelitis (EAE) begins with a similar "vaccine" to cause an autoimmune reaction. In the MS model mice are vaccinated against the myelin protein. Instead of looking at the autoimmune reaction directly in these mice, the T cells are removed and placed into mice that did not receive the "vaccine". In this model, the researchers can specifically look at the autoimmune effects of the T cells and how the drug works to reduce T-cell driven autoimmune disease.

Part of the reason Compugen wanted to look at the T-cell based resonse is because their new drug, CGEN-15001 binds to a receptor on T-cells and blocks the signal that would normally result from receptor binding which would propagate the immune response (in this case the auto-immune response).

A second positive aspect of Compugen's new drug is that the protein is attached to the Fc portion of an antibody. If you imagine an antibody looks like the letter "Y", the Fc portion is the bottom half. So, when the drug/protein part binds to the receptor on the T-cells, the Fc is just sticking off of the cell like a sore thumb. There are certain "cleanup" cells of the immune system that will recognize this Fc sticking off the side of the T-cell as a "Bad Cell" marker. The "cleanup crew" will kill the Fc marked "Bad Cells". The end result means less T-cells driving the autoimmune response and corresponding reduction in symptoms.

How does it affect humans?

These studies are SUPER- preliminary. You never know what can happen before these things get to clinical trials. Also, the animal models are a necessary starting point and can give ideas regarding this drug's activity for treatment of disease in broad terms but at the end of the day, there are differences between mice and humans. Some of these differences might be important to how the drug works. If you consider how differently individual people respond to a drug..... a positive result in a different species does not necessarily translate. But, it doesnt mean that it wont translate either. Another hurdle is regarding the model itself. The model is, well, a model. Although the model for a certain disease might closely approximate a disease and its symptoms, the causal factor between model vs. actual disease is not there. Does it matter? Maybe, maybe not. The answer would likely be different for different diseases and for different causative agents producing the disease state.

Compugen Ltd. has shown some promising results in a mouse model of autoimmune disease. Most drugs in development dont even make it that far. Hopefully, Compugen's positive findings will continue and become an effecive therapy for various immune-dysregulation diseases. There is however, a long road ahead.

I hope that clarified things a little.
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Crohn's Disease Forum » Books, Multimedia, Research & News » Compugen announces initial validation results for two novel immunomodulatory proteins
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