FLT3 and MS

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FLT3 and MS

Postby dignan » Wed Nov 30, 2005 9:33 am

Nice that they are looking at different angles of attack on autoimmune disorders...



Dendritic Cells Offer New Therapeutic Target for Drugs to Treat MS

November 30, 2005 - Newswise - Scientists at the Johns Hopkins Kimmel Cancer Center have found that a gene pathway linked to a deadly form of leukemia may provide a new way to treat autoimmune diseases, including multiple sclerosis. Their tests in cell cultures and mice suggest that blocking the pathway by interfering with a blood cell growth gene, known as FLT3, targets an immune system cell often ignored in favor of T-cell targets in standard therapies.

FLT3, which controls the development of healthy blood cells, was identified as a treatment target in patients with acute myeloid leukemia, a blood cell cancer, several years ago by the same Johns Hopkins investigators. In the current work, the Hopkins team has confirmed that the gene is activated in dendritic cells, whose role is to distribute "look here" information about unwanted foreign invaders to soldiering T-cells.

"Someday, using a drug to block FLT3 gene signaling could stop dendritic cells from triggering harmful responses against a patient's own body," says Donald Small, M.D., Ph.D., professor at the Johns Hopkins Kimmel Cancer Center, whose findings appear in the November 15 issue of the Proceedings of the National Academy of Sciences. Preliminary clinical tests in people with autoimmune diseases with just such a drug could begin in the next year, Small said.

A characteristic of autoimmune diseases is that patients' immune T-cells mistake normal cells in the body for foreign ones. Current therapies, such as steroids, are designed to suppress T-cell responses. But the Hopkins investigators believe that targeting dendritic cells may stop the faulty immune response at a higher "upstream" level since T-cells frequently receive their information from dendritic cells.

Testing their idea, Small and his Hopkins colleague Katherine Whartenby used an experimental compound called CEP-701, already known to block actions of the growth-promoting FLT3 gene, on human dendritic cells and in mice engineered to mimic multiple sclerosis, a disease that causes T-cells to destroy the myelin protein sheath around nerves in the central nervous system. The drug had a similar effect on dendritic cells, causing most of them to die. In the mouse model, investigators found that more of the myelin sheath was preserved in mice treated with CEP-701 than those not treated.

Small cautions that massive die-off of dendritic cells poses a possible risk of immune system suppression, a condition that could leave patients vulnerable to infections or other diseases. "But our studies show that though many dendritic cells were destroyed, some still remained," he said.

Their tests also revealed that mice infected with a potent bacterium survived after treatment with CEP-701. This research was funded by the National Institutes of Health.

Additional authors include Peter A. Calabresi, Erin McCadden, Bao Nguyen, David Kardian, Tianhong Wang, Claudio Mosse and Drew M. Pardoll from Johns Hopkins.

http://www.newswise.com/articles/view/516423/?sc=rsmn
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Postby bromley » Wed Nov 30, 2005 12:05 pm

Thanks Dignan,

It seems that every week another molecule or pathway is identified. But therapies to target the molecules or pathways never seem to follow.

The real problem seems to be the focus on EAE (the mouse model of MS). Given our recent thread on EBV (mounting evidence suggests the virus might play a key role in MS) one must question the use of the current mouse model. Does the mouse get injected with EBV? If not (and EBV is proven to be involved in human MS) then it's likely that the mouse model will be a waste of time (as it has been in the past).


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Postby dignan » Wed Nov 30, 2005 4:27 pm

EAE is a big problem. Researchers know it. There isn't a better animal model around I guess or they'd be using it. I'm not sure which will happen first: a cure for MS, or a better model than EAE, which in my opinion will have to be a computer model, not an animal model.
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