Many researchers believe that multiple sclerosis (MS) is caused by immune system attack on the nervous system. In particular, the immune system is thought to damage the myelin sheath that serves as insulation covering nerve cells. This myelin sheath speeds the transmission of nerve signals. Some Caltech researchers have found that remyelination (rebuilding of the lost insulation) can be done by with a gene therapy that delivers a gene for a protein that promotes growth of neural stem cells.
But myelin, and the specialized cells called oligodendrocytes that make it, become damaged in demyelinating diseases like multiple sclerosis (MS), leaving neurons without their myelin sheaths. As a consequence, the affected neurons can no longer communicate correctly and are prone to damage. Researchers from the California Institute of Technology (Caltech) now believe they have found a way to help the brain replace damaged oligodendrocytes and myelin.
The therapy, which has been successful in promoting remyelination in a mouse model of MS, is outlined in a paper published February 8 in The Journal of Neuroscience.
"We've developed a gene therapy to stimulate production of new oligodendrocytes from stem and progenitor cells—both of which can become more specialized cell types—that are resident in the adult central nervous system," says Benjamin Deverman, a postdoctoral fellow in biology at Caltech and lead author of the paper. "In other words, we're using the brain's own progenitor cells as a way to boost repair."
The therapy uses leukemia inhibitory factor (LIF), a naturally occurring protein that was known to promote the self-renewal of neural stem cells and to reduce immune-cell attacks to myelin in other MS mouse models.
The report mentions this treatment might also be useful for repair of spinal cord nerve damage. It also potentially could benefit all of us as we grow old since myelin sheath deteriorates with age. This fits with a larger pattern: Many gene therapies and stem cell therapies aimed at specific diseases will likely turn out useful for rejuvenation. Any advance in tissue repair is likely to have benefit as a rejuvenation therapy.
One of their challenges is to develop better gene deliver mechanisms. That's one of the big challenges of gene therapy. How to get the genes into cells without getting stopped by the immune system and various natural barriers in the body? Also, how to prevent the genes from damaging chromosomes once they enter cells? Also, how to control dosage? Some cells will get many copies of genes and other cells will get none.
To move the research closer to human clinical trials, the team will work to build better viral vectors for the delivery of LIF. "The way this gene therapy works is to use a virus that can deliver the genetic material—LIF—into cells," explains Patterson. "This kind of delivery has been used before in humans, but the worry is that you can't control the virus. You can't necessarily target the right place, and you can't control how much of the protein is being made."
Gene therapy might find greater usage in the short to medium term to modify cells removed from the body before the cells are introduced back into the body. Basically gene therapy will get used to train cells to work better as cell therapy.
|Share |||Randall Parker, 2012 February 20 09:45 PM Biotech Gene Therapy|