Even if you do not have multiple sclerosis (MS) or know anyone who has MS the research into how to repair myelin sheath (nerve insulation which gets damaged in MS) matters for your own brain's future. As we age our myelin sheath degrades and this contributes to cognitive decline experienced as people get older. Therefore I always cheer on MS research more than research in most diseases. Work at USCF and U Cambridge put to a regulatory pathway as key for telling oligodendrocyte cells to make more myelin.
In this study the researchers have identified the Wnt pathway, which plays an active role in the maintenance and proliferation of stem cells, as a crucial determinant of whether oligodendrocytes can efficiently make myelin. Their studies demonstrate that if the Wnt pathway is abnormally active, then the process is inhibited. This opens up the exciting possibility that the repair can be enhanced in MS patients by drugs that block the Wnt pathway.
Professor Robin Franklin from the University of Cambridge, a co-senior author of the study, explained the significance of their findings: "The pathway we identified plays a critical role in whether repair to the damaged cells will or will not occur. Interestingly, mutations in this particular pathway are also involved in several cancers. In this regard, drugs that inhibit this pathway from signaling have been sought which might suppress tumour growth. These same drugs may also find a role in promoting repair in MS."
Regulatory pathways that control growth are always of interest to cancer researchers. So cancer research work has helped build up information about the Wnt regulatory pathway that helps MS researchers in their own investigations. More generally, cancer research into cell growth regulation helps to build up the knowledge we need to develop a large assortment of cell therapies.
To find out which genes were contributing to three key stages in the repair process – the recruitment of oligodendrocyte precursors to the site of injury, the maturation of those cells into functional oligodendrocytes, and the formation of a new myelin sheath -- they measured the activity of 1,040 genes. All of the genes they studied encode transcription factors, which regulate the activity of other genes. Their experiments showed that 50 transcription factors are working during key steps in myelin repair.
One of the reasons I expect a revolution in biomedical treatments over the next 20 years is the development of chips that can do massively parallel manipulations and measures with cells and cellular components. Biotechnology now benefits from the same shrinking of scale that has done so much to double computer power many times.
The researchers were able to focus on a single gene that might make a good target for drug development.
The team then honed in on a gene called Tcf4, because its expression was strong in damaged areas where repair attempts were under way.
Tcf4 is involved in a cascade of biochemical events known as the Wnt (pronounced "wint") pathway, whose importance has been well recognized in normal development of many tissues, including the brain. Until now, however, Wnt had not been linked to myelin production or repair.
"This is the first evidence implicating the Wnt pathway in multiple sclerosis," says lead author Stephen P.J. Fancy, PhD, a postdoctoral fellow in the Rowitch lab. "We consider this an exciting development in our efforts to understand why the repair process often fails in the disease."
Some of us alive today will live long enough to see tissue repair to become commonplace throughout the body. Development of this capability will slow and eventually reverse the aging process.
|Share |||Randall Parker, 2009 July 02 12:15 PM Biotech Neuron Repair|