Last year, researchers in a multi-institutional study discovered a DNA change found to be the cause of more than 40 percent of inherited and 10 percent of spontaneous cases of amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. Up to this point, no other reliable genetic cause was known for the most common, sporadic form of these progressive neurodegenerative diseases.
By studying how this ALS genetic change affects neurons and glial cells — the neurons' support cells — Johns Hopkins researchers hope to develop new therapies for the disease. The team took skin biopsies from patients with this form of ALS, and converted the skin cells to induced pluripotent stem (iPS) cells — stem cells that can be coaxed into other cell types — and then into neurons and glia using the latest stem cell culture techniques.
First, the researchers examined the extent to which the level of genes in the ALS stem cells were turned up or down in comparison to cells from healthy people. They found at least four genes reliably changed levels in the ALS neurons, and also found the same changes in brain tissue from deceased ALS stem cells. By using gene therapy to add pieces of DNA into the ALS stem cells, the researchers reduced the levels of one of the genes to that of normal neurons.
"These stem cell assays have already allowed use to discover drugs that normalize the gene levels like the gene therapy did to search for ALS treatments," says Jeffrey Rothstein, M.D., Ph.D., director of the Brain Science Institute and the Robert Packard Center for ALS Research at the Johns Hopkins University School of Medicine. "Unfortunately, it's too early to say if restoring the gene levels will treat the disease. But, it's an important lead and an exciting way to approach ALS therapy."
Talk/Program # 517.01, Room 277, Tuesday, Oct. 16, 2012, 8- 8:15 a.m. CSTAuthors: C. J. Donnelly, L. W. Ostrow, P.-W. Zhang, S. Vidensky, N. A. Mistry, U. Balasubramanian, Y. Li, P. Tienari, N. J. Maragakis, B. J. Traynor, R. Sattler, J. D. Rothstein
AND
Poster#: 858.01, Hall F-J, Wednesday, October 17, 2012, 1:00 PM - 2:00 PMAuthors: L. W. Ostrow, C. Donnelly, Y. Li, S. Vidensky, P. Tienari, N. J. Maragakis, B. J. Traynor, J. D. Rothstein