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Toward An Alternative To Stem Cells For Treating Chronic Brain Diseases

Science Daily — With ethical issues concerning use of discarded embryos and technical problems hindering development of stem cell therapies, scientists in Korea are reporting the first successful use of a drug-like molecule to transform human muscle cells into nerve cells. This advance could lead to new treatments for stroke, Alzheimer's disease, Parkinson's disease and other neurological disorders.

In the study, Injae Shin and colleagues point out that stem cell research shows promise for repairing or replacing damaged nerve cells to treat such diseases. However, many barriers hinder efforts to move those therapies from lab to clinic. The use of "small molecules" -- compounds that include most drugs -- to generate new nerve cells from easily available cells or tissues would provide a more convenient and attractive approach to stem cell therapies, the new study notes.

The researchers exposed immature mouse muscle cells (myoblasts) growing in laboratory cell cultures to neurodazine, a synthetic small molecule. After one week, 40-50 percent of the myoblasts were transformed into cells that resembled both the structure and function of nerve cells, including expression of neuron-specific proteins. Additional studies showed a similar transformation in a group of human skeletal muscle cells that were exposed to the same chemical for several days, they add.

"In conclusion, we have developed the first small molecule that can induce neurogenesis of non-pluripotent myoblasts and the cells derived from mature, human skeletal muscle," the report states. "These studies build upon recent research illustrating the value of chemical approaches for providing tools that differentiate lineage-committed cells into other cell types."

http://www.sciencedaily.com/releases/20 ... 172012.htm



The Pubmed abstract about this research:


Synthetic Small Molecules that Induce Neurogenesis in Skeletal Muscle.

J Am Chem Soc. 2007 Aug 1;129(30):9258-9. Epub 2007 Jul 10.
Williams DR, Lee MR, Song YA, Ko SK, Kim GH, Shin I.
Department of Chemistry, Yonsei University, Seoul 120-749, Korea.

Neurons are not regenerated effectively, and their injury causes neurodegenerative diseases. These diseases may be treated by the transplantation of neural stem cells. However, ethical and technical issues restrict cell therapies using neural stem cells. A more convenient and attractive approach is the use of small molecules with the capacity to induce neurogenesis from easily available cells or tissues. Such small molecules have the potential to allow tight controls over the timing and speed of cell differentiation. Herein, we describe the discovery of the first such molecule, neurodazine, identified by screening an imidazole library with C2C12 myoblasts. Further analyses show that neurodazine promotes the expression of neuron-specific markers in treated C2C12 cells. In addition, the use of neurodazines in conjunction with a microtubule-destabilizing agent allows neurogenic conversion of both differentiated immature myotubes and mature skeletal muscle.