Geron: prohibition of the clinical trial with human embryonic cells


Authorisation of the FDA
 
At the beginning of 2009 the Food and Drug Administration (FDA) has granted authorization to Geron Corporation, the leader company in research on embryonic stem cells, for a clinical trial on patients withlesions of spinal cord from a human embryonic cell line (GRNOPC1). This line was created by Geron and is derived from the H1 human embryonic line created on the 9th of August of 2001 and qualified for human use (normal karyotype and free from animal or human contaminants).
For Geron it dealt with initiating a phase I trial which aimed at restoring the functions of the spinal cord with injections, directly on the patient lesion, of oligodendrocyte progenitor cells (cells from the tissue around the nerve cells) derived from human embryonic cells (CSEh). The treatment, quickly given (within the fifteen days following the lesion) should allow regenerating the myelin sheath.
 
Before obtaining the authorization for a phase I clinical trial by the FDA, Geron had to proceed to preclinical studies, with a GRNOPC1 injection in healthy animal populations.
 
This authorization granted by the FDA to the first human clinical trial from human embryonic stem cells aroused enthusiasm in researchers inclined to work on these cells. "We have to be pleased about the authorisation given by the FDA", thought Pr Peschanski, director of I-Stem laboratory. "The lines of SEh oligodendrocyte cells prepared for performing this trial will be at team’s disposal to conduct other trials which will save significant time. We are discussing this theme for a long time with this group and we know that these researchers are open and ready to exchange” he was delighted. Also he noted that France “started with a 7 year delay”.
 
Suspended authorization
 
Yet in August 2009 the FDA suspended the authorisation granted to Geron Corporation, to perform these clinical trials and at the end of 2009, the FDA did not give again its green light. 
 
The company remained vague about the reasons of this suspension. It would seem that it is related to the re-examination of some data on animals. Geron performed indeed 24 studies, conducted separately, on mice and rats. Then it affirmed that all of them had satisfactory results. But some of the animals having microcysts at the injection points of human stem cells, after the delivery of this data to FDA, the decision was taken to postpone the clinical trials and to continue the works on the animal. On the 28th of October of 2009 the positive results of works on the animal were published in Stem Cells, under the signature of Hans S. Keirstead. However we had to emphasize that this work published in Stem Cells is not original, since S. Keirstead repeats these experiments on rats for years. Geron transmitted this new data to the FDA which until now did not answer. 
 
For Evan Snyder, neuroscientist managing the stem cell research centre at Burnham Institute for medical research in San Diego, "there is a great debate among the researchers on spinal cord, because the preclinical data themselves do not justify the clinical trials".
 
No clinical trial with CSEh 
 
It is useful to remind that Geron's studies are limited until now to preclinical studies on the animal, made on rats, because if the announcement of the authorisation by the FDA of a first clinical trial with human embryonic cells was very relieved, the suspension by the FDA of this same trial did not cause commotion… No clinical trial is actually performed with human embryonic cells.
 
It is not the first time that Geron benefits from this type of announcement: the company has already affirmed in 2004 it wanted to conduct clinical trials with glial cells coming from embryonic stem cells for the preparations of lesions of the spinal cord. It had started again the announcement in 2005. These announcements go together with the increase of its stock exchange quotation.
 
Clinical trials without CSEh
 
H. Deda and S. Kocabay’s teams have published in October 2008 very encouraging results of phase I clinical trials on the transplantation of hematopoietic autologous stem cells of bone marrow on nine patients with complete chronic lesion of spinal cord with A-level functional defect. This treatment was found efficient and safe, without complications. The use of autologous stem cells by these authors allows them in particular to avoid the reactions of immunologic rejection and reaction of the graft against the host, as well as the appearance of tumours at the injection points that would also be caused by a transplantation of human embryonic stem cells, according to the model recommended by S. Keirstead from his works on rats.
 
The rich Chinese experience 1 seems to show that the umbilical stem cells, which can be used in patients without problem of immunologic rejection or tumours, would also be more efficient than the marrow bone cells in the treatment of lesions of spinal cord. Moreover they would have the advantage to be able to be applied very quickly after the trauma, thanks to umbilical cord banks.
 
Also we have to note that other positive results obtained from patients, in the treatment of sclerosis en plaques by transplantation of mesenchymatous allogeneic 2 stem cells, or hematopoietic autologous stem cells 3 and by injections of autologous stem cells of bone marrow 4, or stromal stem cells of the vascular fraction of adipose tissue 5. In all these cases the stem cells did not cause negative reaction in these patients and have stopped the course of the disease and gave a clear improvement of their state.
 
We understand that the phase I clinical trial on transplantation of human embryonic stem cells in patients with lesions of spinal cord, like Geron foresees it, is not urgent, since we already have for several years the treatment for lesions of the spinal cord by adult stem cells or umbilical cord stem cells, and that the treatment was found to be sure and effective in patients.
 
1 - Cao FJ, Fang SO, Chin Med J, 20 janvier 2009
2 - J.Liang, L.Subn et al., Mult Scler. mai 2009
3 - R.K.Burt, W.H.Burns, The Lancet Neurology, mars 2009
4 - N.Scolding et al., nov 2009
5-Riordan NH, B.Minev, J. Translational Medicine, 24 avril 2009