Nov. 1 /PRNewswire/ -- Scientists at Children's Hospital Boston have described an important mechanism controlling axon regeneration in nerve cells. Their discovery is reported in today's issue of The Journal of Neuroscience. This work was sponsored in part by Boston Life Sciences, Inc. (Nasdaq: BLSI - news), which is the exclusive commercial licensee of this technology for all therapeutic indications including spinal cord injury, stroke and glaucoma.
``This paper describes for the first time a central program that controls a whole family of genes required for axon growth, and that Inosine can directly switch on this program,'' stated Dr. Larry Benowitz, senior author of the paper. ``We previously published on the extraordinary axon-regenerative properties of Inosine in vivo. These findings help explain why Inosine has such dramatic positive effects after brain and spinal cord injury.''
Normally, central nervous system (CNS) cells are unable to re-grow damaged fibers. Consequently, when such disruption occurs, their communication with other nerve cells is lost, causing debilitating losses in function for victims of stroke or traumatic injury. In a previously published paper (PNAS, November 9, 1999), a group led by Dr. Larry Benowitz reported that Inosine, a naturally occurring small molecule that is normally found in low levels in the brain, can promote extensive axon sprouting in animals with spinal cord injury. In the current paper, Dr. Larry Benowitz (senior author) and co-workers describe the mechanism by which Inosine apparently works. Benowitz and his group are hopeful that by activating neurons with Inosine (as demonstrated in previous in vivo animal studies), they may be able to achieve regenerative axon growth in humans whose central nervous systems have sustained injury in stroke and spinal cord trauma.
The new findings indicate that Inosine passes right through the nerve cell's membrane and activates an enzyme that appears to be the ``master switch'' that controls the cell's molecular program for axon growth (the existence of this enzyme was first suggested by work from the laboratory of Lloyd Greene at Columbia University). This same mechanism is believed to be activated when brain cells are forming their connections during embryonic development. In their studies, Dr. Benowitz and his group found that this Inosine-activated program causes nerve cells to switch on a set of genes that encode the proteins essential for nerve regeneration. In the adult brain, this cellular program is normally silent, and nerve cells that have been injured (e.g. by stroke) are not able to regenerate their axons. Nevertheless, as described in this paper, this genetic program can be reactivated by Inosine. Benowitz's group is close to isolating the actual gene that encodes the enzyme upon which Inosine works. This, in turn, will enable them to gain further valuable and clinically relevant insights into the possibilities for regenerative axon growth in nerve cells.
``We knew from previous studies that there is a whole set of genes that are commonly activated only when nerve cells are forming their connections. However, we didn't know whether the expression of these genes was controlled through separate pathways that are activated by different growth factors, or whether there was a 'master switch', onto which different signals converge to control the entire molecular program for axon growth. Our findings indicate that the regenerative effects of growth factors are mediated through this final common pathway,'' added Dr. Benowitz.
Benowitz, whose work in this area was sponsored by Boston Life Sciences, Inc. and the National Institutes of Health, is the Director of the Laboratories for Neuroscience Research in Neurosurgery at Children's Hospital and a member of the faculty of Harvard Medical School. Other investigators involved in this study included Barbara Petrausch and Claudia Stuermer from the University of Konstanz (Germany), Daniel Goldman from the University of Michigan, and Raymond Tabibiazar, Timo Roser, Yun Jing, and Nina Irwin, members of Benowitz's group at Children's Hospital.... |
