A team of researchers at RIKEN and Kobe City Medical Center reported at a press conference today a serious adverse event in a clinical trial participant receiving an induced pluripotent stem cell (IPS cell)-based therapy for vision loss.
According to Japan Times and Yahoo! Japan (in Japanese), the patient in question in the IPS cell trial for macular degeneration developed a problem with his eye following the cell transplant. From Yahoo! Japan:
“The patient had an operation on Monday to remove pre-retinal membrane, deemed to be the cause of retinal edema, as the team was unable to improve the symptoms despite the administration of a steroid and anti-vascular endothelial growth factor medication.”
You can see an example of an experimental IPS cell-based transplant of RPEs in the team’s important paper from last year above.
The team leader, Dr. Masayo Takahashi indicated in a press conference that:
“We cannot deny the causal correlation with iPS cells,” Masayo Takahashi, a researcher at Riken who heads the team, said at a news conference.
Takahashi said the symptom “falls into the category of serious cases,” as it requires hospital admission for treatment, but that it is “neither a matter of great urgency nor life-threatening.”
I’m not clear if the IPS cell-derived retinal pigmented epithelial (RPE) cells grew or assembled into this “pre-retinal membrane” or it was more related to the injection protocol itself, but the words “causal correlation with iPS cells” suggests they played a role. Update: However, a translation of the Japanese article now suggests the opposite, that perhaps the cells themselves were not an issue:
“Riken project leader, Masayo Takahashi told that she considers the cause of adverse event the surgical method used for cell transplantation, not iPSC itself.”
It’s reassuring that Dr. Takahashi also said the incident should not interfere with the future of the trial:
“She said the incident should not affect the future process of the clinical study of transplantations of iPS-derived retinal cells in patients with severe eye diseases.”
I’m trying to better understand what happened to cause the problem, but need more information to have a better sense of what the implications might be. A quick Internet search of “pre-retinal membrane” suggests it can be due to scarring of the outer surface of the retina.
Notably, Japan’s regenerative medicine law mandates reporting of such adverse events:
“The team made the announcement in accordance with the law requiring medical institutions to report to the Minister of Health, Labor and Welfare a patient’s illness or worsening condition suspected to have been caused by regenerative medical techniques.”
In the past, a different iteration of the IPS cells for vision loss study in Japan was halted reportedly due to regulatory changes and potentially because a patient’s IPS cells had some mutations. Japan’s IPS cell efforts have switched gears in recent years to a more allogeneic (stem cells from other people rather than from yourself, which is called autologous) focus.
As there are more and more stem cell trials of various kinds, adverse events are to be expected, should be reported as this one was, and with proper controls can be understood in terms of risks as products navigate the process.
This all goes to show that stem cell-based clinical trials are more of a non-linear marathon than a sprint from points A to B, whether the clonal work is based on adult, embryonic or IPS cells.
If I hear from Dr. Takahashi on more specifics of what happened and why or get more information another way I’ll update this post or do a new one to follow up.