Blocking the action of a gene in the body may be the basis of the newest therapy for multiple sclerosis and other autoimmune diseases someday. That's the theory of a group of scientists who conducted a series of tests related to the gene.
Their findings appear in the November 15 issue of the Proceedings of the National Academy of Sciences.1
Disrupting a Gene to Treat MS?
The gene is known as FLT3, which targets an immune system cell often ignored in treatment design. Instead, T-cells, included in the cells that make up the immune system and cause inflammation in some cases, are often evaluated as possible treatment targets.
In contrast, FLT3 is a gene that controls the growth of blood cells. Initially, it was evaluated as a possible treatment target for people with leukemia, a blood cell cancer.2
In the latest study, Donald Small, MD, PhD, a professor of Oncology at the Johns Hopkins Kimmel Cancer Center at Johns Hopkins University in Baltimore, and his colleagues confirmed that the gene is active in dendritic cells, whose role is to alert T-cells in the immune system about the presence of foreign pathogens, or disease-causing organisms, in the body.
"Someday, using a drug to block FLT 3 gene signaling could stop dendritic cells from triggering harmful responses against a patient's own body," Small explained.
Immunity Gone Haywire
MS is believed to be an autoimmune disease that targets tissue in a person's central nervous system, the part of the nervous system involving the brain, spinal cord, and optic nerves. Surrounding and protecting nerve fibers in this area is a fatty substance known as myelin. When MS occurs, it's believed that the immune system incorrectly targets myelin and the nerve fibers it protects, damaging them and causing the symptoms that arise in the disease. It's not known why immune system cells do this.
When myelin is stripped away, the ability of the nerves to conduct electrical impulses becomes disrupted.3
Halting an Immune System Gone Bad
In this haywire response of the immune system, T-cells play a significant role in targeting healthy tissue like myelin in the body. Current therapies like steroids target T-cells and suppress their activity. But the investigators in the latest study believe that targeting dendritic cells may halt the faulty immune response earlier in the chain of events since T-cells receive their instructions from dendritic cells.
To test their theory, Small and his colleagues used an experimental compound, which is already known to block the actions of the FLT3 gene, to see if would also hamper the effects of dendritic cells. The tests were carried out in mice that were bred to have a disease similar to MS known as experimental autoimmune encephalomyelitis (EAE). They also conducted their experiments on a group of human dendritic cells.
In the end, Small's team found that the compound did, in fact, block the activity of human dendritic cells, causing most of them to die. In the mice, those given the compound had intact myelin sheaths, whereas those not given the substance had their myelin destroyed due to the disease, the investigators reported.
There is one caveat in this experimental treatment approach, however. Small cautions that massive destruction of dendritic cells may lead to a dangerous level of immune suppression that could leave people susceptible to other diseases or infections. "But our studies show that though many dendritic cells were destroyed, some still remained," he said.
1. Whartenby KA, Calabresi PA, McCadden E et al. Inhibition of FLT3 signaling targets DCs to ameliorate autoimmune disease. Proc Natl Acad Sci USA 2005 Nov 15;102(46):16741-6. Epub 2005 Nov 4.
2. Paz K, Zhu Z. Recent advances in targeted therapy of human myelogenous leukaemia. Expert Opin Ther Targets 2005 Dec; 9(6):1147-63.
3. National Multiple Sclerosis Society. What is Multiple Sclerosis? Available at: http://www.nationalmssociety.org/What%20is%20MS.asp. Accessed December 5, 2005.
John Martin is a long-time health journalist and an editor for CuraScript. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
