New MS Target for Treatment Known
A research team composed of an international group of scientists led by those from the Centre Hospitalier de l’Universite de Montreal (CHUM) has identified new therapeutic targets for the possible treatment of multiple sclerosis. The research can provide fresh answers to questions involving the role of novel adhesion molecules in the pathogenesis of the said debilitating chronic disease of the nervous system.
The research was conducted by Dr. Alexandre Prat, a CHUM neurologist and researcher and a professor at the University of Montreal’s Faculty of Medicine, along with collaborators from McGill University, Dr. S. David, Dr. N. Arbour from the University of Montreal, Dr. D. Stanimirovic of the National Research Council of Canada and Dr. B. Becher of the University of Zurich. The team found that the adhesion molecule known as ALCAM for Activated Leukocyte Cell Adhesion Molecule, otherwise known as CD166, plays a major role in the movement of certain types of leukocytes to the brain.
The researchers believe that the molecule, which is produced by the endothelial cells of the brain, becomes a novel target that helps restrict migration of immune cells to the brain. This can further help dampen neuro-inflammation and decreasing the lesions on the brain that is characteristic of multiple sclerosis. Being able to understand the molecular processes of brain inflammation is important to the development of new treatments for MS.
Genetic Differences May Play a Role in Successful MS Treatments
It may be a wonder for some people as well as doctors why an MS treatment may work well on one patient and not on another. A recent study has shown that genetic differences may explain why some MS patients respond well to certain treatments while some do not. This study will later on help doctors predict which type of treatments will help different patients.According to an article in the Science Daily website, an international collaboration of researchers which included Dr. Esther Byun of the University of California has identified important genetic differences by comparing the DNA of patients with multiple sclerosis that experienced having reduced symptoms following interferon beta therapy and those who experienced relapses given the same treatment. The team of researchers followed a group of 206 Southern European patients with relapsing-remitting MS for two years after they started interferon beta therapy to treat the disease.
During the said study, the researchers collected DNA samples of each patient in the group. And every three months, the patients were checked how they reacted to the treatment by analyzing their disability levels. The study came up with 99 patients who responded well to the interferon beta treatment while the other 107 patients did not. After dividing the group in two, the researchers used micro arrays to identify certain genetic
The researchers were able to identify the top 35 single nucleotide polymorphisms or SNP’s that were candidates for further analysis. SNP’s are variations or changes that occur in a single base of DNA. The researchers then located these SNP’s in each individual patient to see if the mutations seen in those who responded well to treatment differed from those who did not. After this analysis was complete, an additional 81 patients with MS (44 responders and 35 non-responders) were added into the study. The DNA of responders was again compared to that of the non-responders.
The identification of genetic mutations in the patient’s DNA that affect response to interferon can provide researchers with important new information about how the drug functions in the body. This will help bring scientists one step closer to rational drug design and personalized medicine, the authors of the study note. However, there is a need for additional research to fully predict the treatment outcomes that are based on DNA analysis.
Source: http://www.sciencedaily.com/releases/2008/01/080114162520.htm
Modifying Bone Marrow Cells Help Treat Multiple Sclerosis
Another new means of possibly treating multiple sclerosis has been found with the use of modified bone marrow cells. Researchers from the University of Bonn in Germany have been able to genetically engineer bone marrow cells to treat multiple sclerosis by reducing inflammation brought by the disease as well as clearing tissue debris. This treatment may also be used to deliver drugs more effectively into the central nervous system.
A team of scientists from the University of Bonn have been able to modify myeloid precursor cells to express a protein known as TREM2 (triggering receptor expressed on myeloid cells-2) which is made by a cell from the central nervous system. The modified bone marrow cells were then injected into the veins of mice with experimental autoimmune encephalomyelitis or EAE, the animal model for multiple sclerosis.
When injected into the affected mice, the scientists found out that the modified TREM2 expressing myeloid precursor cells migrated into the spinal cord of the animals showing EAE symptoms at their peak. The modified cells also helped reduce EAE symptoms and nerve damage in the affected mice. The treatment also helped halt further myelin loss and cleared up cell debris and damaged myelin fragments. What makes it even more promising is that the modified cells only migrated into the spinal cord of mice with EAE. The said migration was not exhibited in healthy mice injected with the same modified myeloid precursor cells.
Multiple sclerosis is a disease where the immune system itself attacks and destroys the myelin around nerve fibers in the central nervous system. Myelin acts as the insulation around these nerves and damage to them may have an effect on how nerve signals are being transmitted. The disrupted nerve signals causes weakness or paralysis on the limbs. Multiple sclerosis may even affect balance and coordination aside from displaying other physically debilitating symptoms.
One of the major challenges in the treatment of multiple sclerosis is the effective delivery of drugs into the central nervous system, most especially, to the lesion site. The blood-brain barrier can restrict the delivery of drugs into the central nervous system when injected intravenously. The problem can further be worsened by the short half-life of certain therapeutic agents used in the treatment of MS.
One way of resolving this problem is by making use of an organ-targeted protein delivery system as was used in the modified TREM2 expressing myeloid precursor cells that was injected on an animal model to treat EAE. The modified bone marrow cells were able to penetrate into the spinal cord of mice affected with EAE and be treated more effectively. This approach has paved the way for developing an effective means of treating multiple sclerosis in humans in the near future.
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