February 23, 2009, Cambridge, UK - Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a devastating condition in which motor neuron degeneration causes progressive loss of movement and muscle tone, leading to death. Overcoming the limited success of previous models, a report published in Disease Models & Mechanisms (DMM), dmm.biologists.org describes how neurons can be derived from human stem cells, and engineered to mimic inherited ALS.
Researchers at the University of California Los Angeles developed an optimized protocol to generate motor neurons from human embryonic stem cells (ES cells), which express normal or mutant forms of the SOD-1 gene, which is linked to inherited, familial ALS. Resulting cells exhibit hallmark characteristics of motor nerve cells, and neurons expressing mutant SOD-1 display abnormalities typical of ALS. Defects included shortened cell projections and a reduced life span compared to cells containing the normal SOD-1 gene.
This human cell-derived model of ALS provides a new method of studying this disease and testing novel therapeutics. This is especially helpful as only one drug is approved to help slow ALS progression, and animal models currently used in drug development have had limited success. Additionally, this research may aid other gene-linked neurodegenerative diseases, as they too may benefit from studies in a human cell-derived model.
Commentary on this work will be featured in the DMM Podcast for Volume 2, Issue 3/4 of DMM. Podcasts are available via the DMM website at: dmm.biologists.org.
The report was written by Saravanan Karumbayaram, Theresa K. Kelly, Andres A. Paucar, Anne J.T. Roe, Joy A. Umbach, Andrew Charles, Harley I. Kornblum, and Martina Wiedau-Pazos at the David Geffen School of Medicine at the University of California Los Angeles, and Steven A. Goldman at the University of Rochester Medical Center in Rochester, NY. The report is published in the March/April issue of Disease Models & Mechanisms (DMM), a research journal published by The Company of Biologists, a non-profit based in Cambridge, UK.
About Disease Models & Mechanisms:
Disease Models & Mechanisms (DMM) is a new research journal publishing both primary scientific research, as well as review articles, editorials, and research highlights. The journal's mission is to provide a forum for clinicians and scientists to discuss basic science and clinical research related to human disease, disease detection and novel therapies. DMM is published by the Company of Biologists, a non-profit organization based in Cambridge, UK. The Company also publishes the international biology research journals Development, Journal of Cell Science, and The Journal of Experimental Biology. In addition to financing these journals, the Company provides grants to scientific societies and supports other activities including travelling fellowships for junior scientists, workshops and conferences. The world's poorest nations receive free and unrestricted access to the Company's journals.