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October 20, 2009

iPS Cells and the Peak of Inflated Expectations


CREDIT: J. T. Dimos et al., Science, 29 August 2008, p. 1218

by Greg Miller

If you've been reading science news stories for the past couple of years, you've probably heard that induced pluripotent stem (iPS) cells are the next big thing. They have many of the same talents as embryonic stem cells, but they don't carry the ethical baggage. That's because iPS cells don't require the destruction of embryos: They can be created by reprogramming skin or other cells from any adult--including patients with nervous system disorders. Although iPS cells may one day be used as treatments, right now many researchers are using them primarily as research tools. This morning I stopped by a session on iPS cells to get a sense of how things are progressing.

Allison Ebert of the University of Wisconsin, Madison, gave a nice overview of a flurry of recent papers demonstrating the use of iPS cells derived from neurological patients. The first was a 2008 Science paper that used skin cells taken from an 82-year-old woman with amyotrophic lateral sclerosis to create iPS cells and coax them to differentiate into motor neurons. Earlier this year, Ebert and colleagues reported in Nature that they'd derived iPS cells and created motor neurons from a patient with another neuromuscular disorder, spinal motor ataxia (SMA). She and her colleagues are studying these cells for clues about why motor neurons die off in SMA. One early hint, she reported, is that genes involved in apoptosis, or programmed cell death, seem to be upregulated in these cells.

Ricardo Dolmetsch of Stanford spoke about his group's efforts to create iPS cells from patients with a variety of autism-related disorders and examine the resulting neurons for abnormalities in gene expression, fine-scale anatomy, and electrophysiology. Jason Chiang, a fifth-year graduate student at Johns Hopkins University, described his work with iPS cells from two people with trisomy 13, a profoundly debilitating neurodevelopmental disorder for which there is no good animal model. Chiang presented evidence that defects in cell signaling pathways involving Wnt proteins, key regulators of neural development, may be involved in the neurological aspects of the disorder.

Dolmetsch summed up the state of the field at the end of his talk, throwing up a slide from a tech consulting firm that traces (in a slightly tongue-in-cheek fashion) the stages of a new technology as it progresses from the "peak of inflated expectations" to the "trough of disillusionment" to the "slope of enlightenment," finally arriving at the "plateau of productivity." Dolmetsch used a laser pointer to indicate where he sees the field: just beginning to come down from the peak.

That seems about right. Despite the great potential iPS cells hold for unraveling the biology of neuropsychiatric disorders and testing potential treatments, many serious questions remain, not the least is how well the findings will translate to real patients. As Dolmetsch said: "I hope the trough isn't too deep."