Patricia F. Fitzpatrick Dimond Ph.D. Technical Editor of Clinical OMICs President of BioInsight Communications

Positive results from new studies show that ESCs still hold much potential for regenerative medicine.

Embryonic stem cell science got a boost this month as Advanced Cell Technology announced on January 8 that investigators for its Phase I/II clinical trials for its human embryonic stem cell product could help rebuild the cells that support photoreceptors in eyes of individuals with certain types of blindness.

The company said that investigators studying Stargardt’s retinal dystrophy (SMD) and dry age-related macular degeneration (dry AMD) reported evidence of engraftment of the transplanted human embryonic stem cell (hESC)-derived retinal pigment epithelial (RPE) cells. The company also reported that the scientists saw signs of visual acuity gain in patients treated over the 18 months since the trials were first initiated.

Commenting on the findings, ACT chairman and CEO Gary Rabin said, “In addition, we have observed persisting engraftment of the transplanted RPE cells in our more recent SMD and dry AMD patients. This is the first time we have shown this in dry AMD patients, which we find particularly encouraging, given that dry AMD represents one of the largest unmet medical needs in the world.”

And in good news for the hES cell field, early this January the U.S. Supreme Court refused to review a challenge to federal funding of human embryonic stem cell research brought by two researchers who said the NIH’s rules on such studies violate federal law. The decision ends the lawsuit that had threatened to hamper stem cell research after a district court judge blocked the taxpayer funding in 2010.

But will the Supreme Court decision encourage more companies to get into testing hES cells for human therapeutic use? To date, ACT remains the one and only active clinical trial testing hES cells as therapeutics.


The only other hES cell company to have had a horse in this race was pioneering Geron, which in 2010, after a long struggle to win permission from the Food and Drug Administration, started the first clinical trial of a therapy derived from embryonic stem cells in spinal cord patients.

In the Geron trial, nervous system cells derived from the company’s flagship product, GRNOPC1—a population of living cells containing oligodendrocyte progenitor cells (OPC)—were injected into people with severe spinal cord injury.

Geron CEO John A. Scarlett, M.D., said that while there were “no signs” that the treatment was helping the patients, signs of efficacy that were not expected in the safety-focused initial trial. And as he noted, so far, he said, there had been no sign of safety problems.

The company shut down its stem cell therapeutics programs in 2011 to conserve funds, planning it said to lay off 38% of its 175 person staff and to seek partners for the program’s assets. Geron abandoned the $25 million effort, after its clinical trial had continued long enough to establish the safety of an ES-cell based product, but no signs of clinical benefit.

The Geron trial discontinuation was perceived as a major setback for the eHS cell field because of the company’s pioneering role. The company had helped support the initial derivation of human embryonic stem cells at the University of Wisconsin in the late 1990s, giving the company fundamental patent rights in the field.

Geron said that its move did not reflect a lack of promise for the controversial field, but that with scarce resources it had decided to focus on its experimental cancer therapies, which are further along in development. “I deeply believe in the promise of stem cells,” Dr. Scarlett said in an interview. “I don’t think that promise is in any way, shape, or form changed by what we’re doing.”

Meanwhile, ACT says that one of its investigative partners filed an Investigative New Drug (IND) application with the FDA to initiate a Phase I/II human clinical trial using retinal pigment epithelial (RPE) cells derived from human embryonic stem cells (hESCs) to treat a severe form of myopia.

For the moment, only ACT remains the real player in the hES cell business. And as Geron exited stem cell therapeutics to become a commodities company, Robert Lanza, M.D., the CSO of Advanced Cell Technology, said Geron’s move was “very unfortunate for the field” and “puts the pressure on us now.”

Potential Treatment for Hearing Loss

But other new findings may impact regenerative medicine and the future of hES cells as new applications for these cells emerge. Last year researchers showed they could use hES cells to restore hearing in gerbils. The model of hearing loss they treated in the gerbils is similar to auditory neuropathy in humans, where damage to the cochlear nerve (also known as auditory or acoustic nerve) disrupts or prevents sound signals picked up by the cochlea in the inner ear from reaching the brain.

In a paper that appeared in the December 9 issue of Nature, Marcelo Rivolta, M.D., Ph.D., and colleagues at the University of Sheffield describe their method for producing both ear hair cells and auditory neurons from human embryonic stem cells. For this study, the team treated stem cells with two types of fibroblast growth factor, FGF3 and FGF10, allowing the development of two types of primordial sensory cell: otic epithelial progenitors (OEPs), which are like hair cells, and otic neural progenitors (ONPs), which are like neurons.

They then transplanted only the ONPs into the ears of gerbils treated with ouabain, a chemical that damages auditory nerves, but not hair cells. Ten weeks later, some of the transplanted cells had grown projections that connected to the brain stem.

Dr. Rivolta said, “We developed a method to drive human embryonic stem cells to produce both hair cells and neurons, or nerve cells, but we only transplanted the neurons. We then used a technique called auditory brainstem evoked responses (ABR), which measures if the brain can perceive an electrical signal after sound stimulation. The responses of the treated animals were substantially better than those untreated, although the range of improvement was broad. Some subjects did very well, while in others recovery was poor.”

These and similar efforts—and a more hospitable regulatory climate—could bring back the hES cell field to fulfill its promise in regenerative medicine.

Patricia Fitzpatrick Dimond, Ph.D. ([email protected]), is technical editor at Genetic Engineering & Biotechnology News.

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