Takahashi team IPS cell vision paper marks major stem cell milestone

Ring the bell for a stem cell milestone.

There’s been a whole lot of commotion about the NEJM article yesterday documenting the experiences of three women with macular degeneration who were blinded by non-FDA approved stem cell eye injections of fat stem cells at a business in Florida, but in the same issue of the journal there also was some encouraging stem cell news that came in the form of essentially a mirror image of the bad news paper. We can call it the “stem cell good news-bad news” issue of NEJM.

Takahashi IPS transplant

Mandai, et al. NEJM 2017 Figure 1C

The good news was the publication of the first paper on clinical use of IPS cell-derivatives in a human patient. A big milestone. This groundbreaking manuscript comes from the pioneering team in Japan led by stem cell scholar Dr. Masayo Takahashi. I’ve written extensively in the past about the work of Takahashi and her team with IPS cells, and she received my Stem Cell Person of the Year Award back in 2014.

In the new paper they detail their data from the clinical study using sheets of retinal pigmented epithelial cells (RPEs) made from IPS cells in this case derived from the patient herself for autologous use. Remarkably in Figure 1C (above) you can see the actual transplanted RPE sheet in the eye of the patient (see dark area indicated by white arrow). The most encouraging part of this study was that the patient’s vision remained stable (rather than declining as expected) following the treatment. Was that due to the transplant? We can’t be sure.

Also, this is just a beginning as it is just one patient, but it is very exciting and represents a big milestone for the IPS cell and broader stem cell field, providing real hope for patients with vision loss along with parallel ESC-based clinical trial work as well.

This paper contrasts so much with the report from the other one in the same issue on the terrible outcomes from the stem cell clinic’s use of fat stem cells in the eye. While the use of fat stem cells themselves is highly questionable in my view for this application, the biggest differences between the two approaches is that the Takahashi team work was extremely rigorous, careful, based on extensive preclinical studies, had governmental approval, and was in essence science-based clinical medicine.

For instance, the Takahashi team was appropriately cautious with Patient 2 since the cells exhibited some genomic changes. At least in part for that reason, moving forward this clinical work will primarily focus on allogeneic use of IPS cells via an IPS cell bank being developed by Shinya Yamanaka.

We can also look to other future IPS cell-based trials coming on-line including for Parkinson’s Disease and other conditions, which are likely to be allogeneic as well in Japan, but probably autologous here in the U.S.

I love a good stem cell milestone!

Japan IPS cell trial for vision to start in new incarnation

Masayo Takahashi, IPS cell trialIt’s been a long road, but the first ever IPS cell clinical study in humans is starting up again in a new incarnation. You might say it has been regenerated in a novel form.

Masayo Takahashi (高橋 政代) first started the pioneering IPS cell study a few years back in 2014, but it ended up getting put on hold in the summer of 2015 in the midst of changing regs in Japan and the discovery of some mutations in the IPS cell derivatives.

About a year after the hold was put in place, we got news that the study would be restarted in a new incarnation, and now more definitively the study is on track to start up again with 5 patients in Japan with the wet type of macular degeneration.  You can read the RIKEN PR here.

The PR provides more info including a co-leader:

“The project will be led by Yasuo Kurimoto and Masayo Takahashi of Kobe City Medical Center General Hospital, and Osaka University’s Graduate School of Medicine/ Faculty of Medicine, and will be conducted in collaboration with the RIKEN Center for Developmental Biology (CDB) and Kyoto University’s Center for iPS Cell Research and Application (CiRA).”

This is great news.

Yasuo Kurimoto is the surgeon who did the initial surgery in the study before it stopped.

One of the most striking things about the new form of this IPSC study is that it will reportedly focus on allogeneic use of IPSC rather than autologous. The foundation for this switch is that allogeneic cells derived from the IPSC can be used in matched recipients and in a relatively genetically homogenous population such allogeneic cells can be used in a number of patients with a good possibility that there won’t be rejection of the transplant.

Embryonic stem cell-based therapies can be used in the same allogeneic way and those are being studied for macular degeneration as well. I still feel like in the long run that the most power and unique positive contribution from IPSC clinically speaking may come from autologous use, especially in diverse populations such as the U.S. Their use in disease modeling is quite impactful as well.

Nominations open for Stem Cell Person of the Year 2016 Award

Nominations are open starting today for the Stem Cell Person of the Year Award for 2016. Please email me your nominations: knoepflerATucdavisDOTedu.stem-cell-person-of-the-year-award

This is a unique award as it is given to an individual who has taken risks to help others within the stem cell field and they based their actions on outside-the-box thinking.

Another unusual aspect is that anyone is eligible for the prize whether you are a scientist, physician, patient, writer, student, etc. There are also no geographic restrictions.

The winner receives recognition as a positive leader in this arena and a $2,000 cash prize that I award myself out of pocket.

Nominations will close one month from today on October 15th.

The nominations I receive will then be subject to an Internet vote and the top 50% will be the finalists, from which I will choose the winner. While I alone choose the winner, I often get feedback from leaders around the globe in the stem cell and regenerative medicine field.

Previous winners include these stellar stem cell leaders:

Who will win the Stem Cell Person of the Year Award for 2016? Send me your nominations.

Stem cell treatment cost 2.0: legit therapy

stem cells costWe hear so much about exciting potential stem cell therapies. Some of these are rigorously evaluated ones in the FDA clinical trial pipeline and others are available right now mainly through predatory stem cell clinics. Earlier this year I posted about the cost of the offerings of dubious stem cell clinics.

In this post, I address the cost of a future, legitimate, FDA-approved stem cell therapy. How high will that be?

This is a critical question because if many patients cannot afford a stem cell therapy then the impact of that therapy is reduced. Cost is inversely related to access. On the other hand, stem cell biotechs must make some profit or they will go out of business. Investors, who are often enthusiastic boosters of the stem cell field, will lose large sums of money and confidence in the field too in that scenario if stem cell treatments are priced “too low”. What is the “right” price?

There is likely to be increasing pressure on biologics drug prices as well from the federal government. Witness Hillary Clinton’s recent tweet on this topic below that sent people into a tizzy.

At the state level, such as here in California, the question of stem cell treatment cost is also becoming more pressing including for our state stem cell agency, CIRM. As CIRM-funded clinical trials advance, which is a wonderful thing, at the same time we get closer to where someone will have to decide on stem cell price tags.

We can look at what other cellular drugs have cost as guidance for the price tag range for stem cell treatments. For instance, Prochymal (its old name under Osiris) that is now rebranded as TEMCELL from Mesoblast/JCR likely will cost about $200K for a full treatment for GVHD (HT to Alexey). Provenge, the cellular prostate cancer drug from the controversial biotech Dendreon had (has?) a price tag of $93K. The most expensive drug in history, the gene therapy med Glybera will cost around $1.5 million per patient.

Realistically, a typical legit stem cell therapy could easily be $100K per patient. A personalized cellular medicine such as an autologous stem cell-based therapy could easily run into the hundreds of thousands per patient. Some therapies could go as high as $500,000 (see this helpful piece by David Jensen) or even into the millions.

Irv Arons

Irv Arons (@iarons) has come up with a great table of cost estimates focused in the area of vision therapy (free registration required). Thanks to Irv for permission to use it here (above).

How will patients afford such expensive therapies?

Will such therapies be covered by governmental agencies or insurance companies? They should.

We should also be keeping in mind the current costs of treating today’s patients with major and sometimes chronic diseases. These costs run into the hundreds of billions or above a trillion dollars each year in the US alone. That’s important context and rightly indicates that the costs of stem cell therapies to society may be appropriate even if at an individual level they seem high.

How does this compare to stem cell treatments at predatory clinics?

Such “treatments” range from $5,000-$20,000 each and most patients with whom I have talked either received or were pitched at least two such treatments, amplifying the total cost. The cost to the clinic of the treatment itself can be as low as $500-$1,000. Some clinics claim to have treated thousands of patients suggesting they are making millions in profits.

Why are stem cell clinic offerings typically relatively cheaper than legit treatments? Frankly, it is because they don’t follow the rules or do the necessary studies to prove safety and efficacy. Ten thousand dollars is still a lot to pay for something that doesn’t work and could even be harmful.

Even so some consumers may perceive dubious stem cell treatments as the way to go because of the lower cost, particularly if the legitimate stem cell field fails to do a good job at educational outreach and the FDA continues to effectively do nothing about the stem cell clinic problem.

The bottom line remains a question. Where’s the stem cell price sweet spot where we can help the most patients, but also generate a needed profit for the biotechs?

We need to find an answer to this question soon.

Stem Cell Person of the Year 2014: Masayo Takahashi (高橋 政代)

Masayo Takahashi

Dr. Masayo Takahashi,  Asahi photo

Congratulations to Masayo Takahashi (高橋 政代), MD, PhD, the winner of the 2014 Stem Cell Person of the Year Award.

Dr. Takahashi received this award including the $2,000 prize for her exceptional achievements in stem cell research in 2014. She was selected as the winner from a stellar group of top 12 finalists this year.

Takahashi leads a team doing high-risk, high reward research that is conducting the first induced pluripotent stem cell (IPSC) clinical study in humans ever. I interviewed Takahashi at the beginning of this year and you can learn more about her research and vision for the future from reading that interviewMonkey stem cell RPEs

The Takahashi team clinical study is intended to examine the safety of a human retinal pigmented epithelial cell (RPE) product made from each patients’ own IPSCs. You can see at right RPEs produced by her team from monkey pluripotent stem cells.

In an astonishing feat of speedy clinical translation, Takahashi’s team transplanted its first macular degeneration patient recently on September 12, only 7 years after human IPSCs were first ever published. The usual timeline for such translation would be 20 years. In that regard, in a recent interview I did with him, Nobel Laureate Shinya Yamanaka had this to say of Takahashi and her work:

I was surprised that after the announcement of human iPSCs in 2007, Dr. Takahashi told me that she would bring iPSC to the bedside within five years. I thought it possible technically speaking, but doubted it could be done so soon, since we needed to improve the technology and get government approval. It took 7 years, which is remarkable considering the work required. Both the accomplishment and the speed at which it was achieved are testaments to Dr. Takahashi’s leadership and her strong team.

Her achievements extend beyond this year to an outstanding long-term track record in vision research including a very impressive track record of highly-cited publications. Takahashi is physician scientist, who is a faculty member and Project Leader at the Laboratory of Retinal Regeneration at the CDB at RIKEN. Some of her nominators for the Stem Cell Person of the Year Award described her as a “transformative” and “courageous” stem cell scientist. Below you can see a TEDx talk from just a few months ago by Takahashi explaining her work.

Takahashi joins previous Stem Cell Person of the Year Award recipients Roman Reed and Elena Cattaneo as outside-the-box thinkers who to take risks to make outstanding new developments in the arena of stem cell research with the goal of helping others.

More about the Stem Cell Person of the Year Award. I fund this prize myself as a way of giving back to the stem cell community and recognizing transformative people who take risks to help others. It is to my knowledge the only annual, international science-related prize personally funded by a professor.