As many of you know, the pioneering, first of its kind IPSC clinical study in Japan has been suspended as I first blogged about here.
In the comments section of that blog post there has been a helpful overall discussion that has involved Dr. Masayo Takahashi, the leader of the trial. It is great that Dr. Takahashi has been participating in this discussion and I commend her for that openness.
This comment stream has been particularly important because the media have only minimally reported on this important development. There have been only a few articles in Japanese (several months ago) and as far as I know only one in English, which was posted in the last day or so in The New Scientist. Unfortunately The New Scientist article, as many have noted here, used an inflammatory title invoking a supposed “cancer scare” and some over-the-top language. Although that article had some bits of important info, the negative bias in the article made it overall not very helpful. Some readers of that article were likely confused by how it was written and the title.
The clinical study in question is for macular degeneration and involves the use of sheets of retinal pigmented epithelial cells (RPE) made from IPSC (e.g. see image above from RIKEN). Several of us have been discussing the suspension of this trial over on Twitter too including Dr. Takahashi (@masayomasayo). Some tweets by the community have been constructive. Others not so much.
Two main possible issues have come up in the discussion of the reasons for the trial stopping: (1) six mutations were detected in the 2nd patient’s IPSC and (2) significant regulatory changes are on the way in Japan that apparently in some way will delimit IPSC research there. Dr. Takahashi has indicated that the latter reason was the dominant factor in their decision to suspend the trial. The fact that the 2nd patient’s IPSC reportedly had six mutations that were not present in the original somatic cells warrants further discussion too. For example, when and how did these mutations arise? To be clear, however, I do not see (based on the information available) that there was a “cancer scare” by any stretch of the imagination as The New Scientist article had indicated.
At some point a restarted version of this study will likely focus on allogeneic use of IPSC perhaps via an IPSC bank being developed by Dr. Shinya Yamanaka. For many years the consensus, most exciting aspect of IPSCs in the field was considered to be their potential for use as the basis for powerful patient-specific autologous therapies. The apparent planned shift to non-autologous clinical use of IPSC in this case raises the question of how it would be superior or substantially different to the use of hESC, other than that making IPSC does not involve the use of a leftover IVF embryo.
This development also raises a 2nd question as to whether there will be a domino effect now of other clinical studies or trials that are in the works using IPSC switching to allogeneic paths as well. In other words, is this a historic, turning point moment for the IPSC field in Japan overall away from an autologous path? Or is the switch here to allogeneic just a one time, one study decision? More info on the regulatory changes is needed to help clarify the answer to this question and the path forward as well.
Hopefully the regulatory body in Japan (Ministry of Education?) that has made or is making the relevant regulatory changes will announce them publicly in detail soon. If that information is already out there (e.g. in Japanese on the web) perhaps someone can find it and we’ll post it here.