By Tom Still

It’s an enduring complaint about human embryonic stem cell research, often but not exclusively voiced by people opposed on moral grounds: If this research is so promising, why is it taking so long to produce treatments?

The long-term answer may emerge in a human clinical trial of a stem-cell therapy for spinal cord injuries – a therapy developed from a line of cells first cultured in Wisconsin.


Geron Corp. announced July 30 that a new drug, derived from human embryonic stem cells, has been cleared to begin clinical trials in patients stricken by acute spinal cord injuries. The trials were delayed last year by the U.S. Food and Drug Administration when one batch of mouse experiments showed cyst growth around the spinal cord injury. Additional animal trials convinced the FDA it was safe to proceed with Phase 1 trials, the first of three phases required before the drug is marketed. Those trials will begin soon in up to seven U.S. medical centers.


In addition to its potential to heal crippling spinal cord injuries in patients with fresh injuries, a dramatic result of the animal trials, Geron’s GRNOPC1 compound may eventually be tested for other applications: Alzheimer’s disease, multiple sclerosis and Canavan Disease, which can be fatal to children.


While it’s possible Geron’s drug won’t work in humans, the start of testing will likely break the logjam for other trials of drugs and therapies derived from human embryonic stem cells.


“It’s great and important news for the whole industry,” said Carl Gulbrandsen, managing director of the Wisconsin Alumni Research Foundation. After UW-Madison professor James Thomson pioneered human embryonic stem cell research, WARF obtained defining patents on that work and has since licensed federally approved stem cell lines to researchers and companies around the world – including California-based Geron.


Thomson was the first in the world to isolate human embryonic stem cells and keep them alive indefinitely in culture, a 1998 discovery the journal Science later described as one of the major milestones in the history of science.

His discovery ushered in a new era of human biological research, providing scientists with “blank slate” cells capable of becoming any of the more than 200 specialized cells in the body and offering researchers a rare view into the earliest stages of human development.


The blank-slate cells used by Geron are from WARF’s federally approved H1 line, which Gulbrandsen described as “a very, very safe line” used by researchers worldwide. The FDA go-ahead for Geron’s trials means others are now eager to sign licensing agreements with WARF, he said.


“We’ve seen another uptick in licensing activity because of (the FDA clearance for Geron),” Gulbrandsen said. “We’ve seen people who have been working for a long time in this field saying, ‘OK, let’s get this done’.”


As a result, other embryonic stem cell therapies may now move closer to clinical trials. Therapies on the horizon target diabetes, Parkinson’s disease, cardiac disease, eye disorders and even production of blood.


“Because this FDA hold has now been lifted, I suspect you’ll see more (Investigational New Drug) applications filed for human embryonic stem cell trials,” said Gulbrandsen, who credited Geron for addressing FDA’s concerns through a “a ton of hard work.”


It took 12 years to move from discovery to the first human trial. So, don’t critics have a point when they say human embryonic stem cells are largely a giant research project?


Not so, countered Gulbrandsen, who noted most non-stem cell drugs require a decade or more to move from the laboratory to the marketplace.


“This is essentially a new industry. If you look at a traditional pharmaceutical, it easily takes 10 years or more to get it approved,” he said. “This is far more complicated… it has required the development of entirely new tools and techniques.”


A successful trial using embryonic stem cells would also hasten the day when trials can begin for therapies from “induced pluripotent stem cells,” which scientists believe can perform in the same ways. Again, Wisconsin holds an edge thanks to next-generation work by Thomson and others who have reverse-engineered IPS cells without destroying embryos.


Why is it taking so long to produce therapies from human embryonic stem cell research? It’s hard scientific work and opponents haven’t made it any easier. If the Geron trials succeed, however, all that work may begin to pay off for patients and researchers alike.


Still is president of the Wisconsin Technology Council. He is the former associate editor of the Wisconsin State Journal.