New Tool a Boon to ALS Researchers

By Reuters Staff

NEW YORK (Reuters Health) - Researchers studying amyotrophic lateral sclerosis have a new resource: a comprehensive library of familial ALS patient-specific induced pluripotent stem cells (fALS- iPSCs).

"We believe this widely available fALS-iPSC library will provide a great tool to study ALS pathophysiology, for biomarker development and for the preclinical development of novel therapies," say Dr. Jeffrey Rothstein and colleagues from Johns Hopkins University in Baltimore, Maryland, who generated the library, in a paper online March 11 in PLOS ONE.

The fALS-iPSCs and their parental fibroblasts are publicly available to academic and commercial entities alike. The fibroblast lines were described in PLOS ONE in 2012 (https://bit.ly/1MNVmfR).

These fALS-iPSCs carry a large variety of ALS mutations and can be differentiated to astroglia, "a critical cell type that plays a role in ALS progression," the researchers say.

"The astroglia derived from this fALS-iPSC library represent the natural disease in terms of allelic copies of the mutant gene, which would provide a faithful model to study cell-cell interactions responsible for disease pathophysiology in ALS and astroglia pathophysiology," they note.

The library is based on the "more common" different ALS mutations, including SOD1 and FUS, and several lines of the same mutation are collected from different families, they point out.

The fALS-iPS derived cells "offer a valuable tool for screening and validating CNS compounds," they further note. "Candidate compounds for treating CNS defects fail in clinical trials in over 90% of cases due to poor targeting, lack of efficacy, and unacceptable side effects. Recent studies using ALS motor neurons derived from iPSCs with mutant TDP43 or SOD1 were successfully used in drug screening, supporting the use of iPSC cell culture platforms for drug discovery efforts."

Creation of the fALS-iPSCs library was funded by the National Institutes Health, through the American Recovery and Reinvestment Act (ARRA). The NIH is also funding development of well-characterized and publicly available iPSCs from familial forms of Parkinson's disease and Huntington's disease.

SOURCE: https://bit.ly/1x5CFRb

PLOS ONE 2015.

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