Overcoming the limited success of previous models, a report published in Disease Models & Mechanisms (DMM), dmm.biologists 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.

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The results by Balic et al "add substantial information on the HRM-based DNA methylation analysis and demonstrate its applicability for analysis of archival tissues." This assay can be used to establish risk stratification of patients based on methylation status of specific markers and, due to its high sensitivity may have the potential to detect low amounts of methylated cells within the tumor, or even to detect low numbers of tumor cells in the background of non-tumor cells in lymph nodes and other organs. Most importantly, because formalin fixation and paraffin embedding are the most common means of tissue storage, the reported method has the potential to make DNA methylation analysis possible on this vast tissue resource.

Balic and colleagues will now evaluate the ability of HRM-based DNA methylation analysis to predict the presence of lymph node metastases and to detect very small tumor deposits in lymph nodes with known micrometastatic disease in a well defined cohort of prostate cancer samples. This may lead to new and better predictive and staging methods for prostate cancer patients.

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