For more than a decade now embryonic stem cell research has been one of the most high profile – and indeed controversial – areas of medical science, and it is an emerging field that owes a lot to animal studies performed by pioneers like Gail Martin of UCSF.
Recently the field has begun to live up to its promise with the announcement last year that the first patient had been enrolled in the first ever clinical trial of a human embryonic stem cells (hESCs), a trial that seeks to evaluate the safety of the hESC-derived oligodentrocyte progenitor cells in patients with spinal cord injury. We discussed the role of animal research in the development of this therapy by Geron Corp in a post on this blog back in 2009.
In September of this year embryonic stem cells were in the news again with the announcement that clinical trials of retinal pigment epithelial cells (RPEs) derived from hESCs for the treatment of an inherited form of blindness known as Stargart’s Macular Dystrophy, are taking place at Moorfields Eye Hospital in London and the Jules Stein Eye Institute at UCLA. The development of this therapy was led by Professor Robert Lanza, Chief Scientific Officer at Advanced Cell Technology, and Adjunct Professor at Wake Forest University School of Medicine, and rests on animal studies which showed that RPE cells derived from hESCs were safe and could restore vision in rodent models of Stargart’s Macular Dystrophy, as a study publishes in the Journal Stem Cells in 2009 makes clear:
Assessments of safety and efficacy are crucial before human ESC (hESC) therapies can move into the clinic. Two important early potential hESC applications are the use of retinal pigment epithelium (RPE) for the treatment of age-related macular degeneration and Stargardt disease, an untreatable form of macular dystrophy that leads to early-onset blindness. Here we show long-term functional rescue using hESC-derived RPE in both the RCS rat and Elov14 mouse, which are animal models of retinal degeneration and Stargardt, respectively. Good Manufacturing Practice-compliant hESC-RPE survived subretinal transplantation in RCS rats for prolonged periods (>220 days). The cells sustained visual function and photoreceptor integrity in a dose-dependent fashion without teratoma formation or untoward pathological reactions. Near-normal functional measurements were recorded at >60 days survival in RCS rats. To further address safety concerns, a Good Laboratory Practice-compliant study was carried out in the NIH III immune-deficient mouse model. Long-term data (spanning the life of the animals) showed no gross or microscopic evidence of teratoma/tumor formation after subretinal hESC-RPE transplantation. These results suggest that hESCs could serve as a potentially safe and inexhaustible source of RPE for the efficacious treatment of a range of retinal degenerative diseases.”
Spinal Injury and Stargart’s Macular Dystrophy are only two of many diseases where hESC based treatments are offering hope of improvement, for more than a decade scientists have been investigating in animal models the use of embryonic stem cells to treat Parkinson’s disease, a degenerative disorder caused by the loss of nerve cells in the brain that produce the neurotransmitter dopamine and results in severe movement impairment. Now, a report in the Guardian newspaper describes how, after years of dedicated research, scientists have overcome a major of technical hurdle and paved the way for the evaluation of hESC therapy for Parkinson’s disease in human clinical trials. The Guardian report stresses the importance of studies in mice, rats and monkeys to evaluating the efficacy and safety of hESC-derived dopamine producing cells:
In a series of experiments, the team gave animals six injections of more than a million cells each, to parts of the brain affected by Parkinson’s. The neurons survived, formed new connections and restored lost movement in mouse, rat and monkey models of the disease, with no sign of tumour development. The improvement in monkeys was crucial, as the rodent brains required fewer working neurons to overcome their symptoms”
The study, which those with a subscription to Nature can read here, is very promising, and hopefully it won’t be very long until we are reading about the start of another clinical trial of hESC derived cells.
It is worth noting that despite fierce opposition from its opponents, public support for human embryonic stem cell research remains very high, a level of support that owes much to the willingness of scientists and research charities such as the Michael J. Fox Foundation for Parkinson’s Research to speak out in support of this important work. While polls indicate that a clear majority of Americans support animal research, that majority could be larger, and the lesson from the stem cell debate is that the public are willing to listen to the arguments put forward by scientist. It is up to all of us who value animal research to do our bit to ensure that the majority in favor of animal research grows; after all, it can’t be right that more Americans support hESC medicine than support the animal research on which it depends!
Paul Browne
Speaking of Research 