While curative stem cell therapies may be years away, scientists say that conditions are ripe to harness the power of certain stem cells in large-scale drug screening.

A team at Sloan-Kettering Institute for Cancer Research and the Institute for Cell Engineering at Johns Hopkins University have taken skin cells of patients suffering from a rare genetic disorder, familial dysautonomia (FD), and created neural crest stem cells containing the single mutation that causes 99.5 percent of FD cases.

Using the created stem cells, the team successfully found a compound that recovered the mutation of the diseased protein by compiling and screening a library of structurally diverse bioactive compounds covering drugs approved by the U.S. Food and Drug Administration.

“Using those stem cells, we can understand human genetic disorders and how those symptoms are presenting,” says Gabsang Lee, Assistant Professor of Neurology and Neuroscience at Johns Hopkins, “We can also use those cells for high-throughput screening in an individualized manner.”

Critical to their success was to establish growth conditions for the diseased neural crest cells that would allow these induced pluripotent stem cells (iPSCs) to tolerate the large scale expansion, freezing, storing and thawing necessary for drug development, the team says in a paper about the work published in the journal Nature.

Since the first reports on establishing human iPSCs, the use of disease-specific cells for drug validation and drug discovery has been an important goal. “There are many rare, ‘orphan’ genetic diseases that will never be addressed through the costly current model of drug development,” Lee explains. “We’ve shown that there may be another way forward to treat these illnesses.”

The group has shown that it is feasible to perform primary screens in iPSC-derived cells for thousands of clinically relevant compounds and they suggest that development of iPSC-based assays for other rare diseases could “contribute to rational clinical trial design and herald an emerging drug discovery approach that moves us closer to an era of personalized medicine.”

This is especially critical for rare neurological diseases, where large numbers of diseased cells are difficult to obtain and the market for a potential therapy is small.

Also in November, another team reported the first mouse model of FD. Although the genetic mutation in FD was identified in 2001, mouse models that accurately mimic the disease have been difficult to establish. The group leading the animal study found that slight increases in the amount of the mutated protein were enough to improve the animal’s symptoms and increase its life span. The animal model, together with the drug screening effort, is certain to accelerate treatment discoveries for this hereditary disease.