Cynata approval for 1st ever allo trial of IPSC-derived MSCs for GVHD

cynataCynata Therapeutics Limited has received approval from UK regulators to start a first-of-its-kind allogeneic IPSC-based trial of MSCs for graft versus host disease (GVHD). Cynata also had some big news a couple weeks back with a deal with Fujifilm.

The company is aiming to recruit 16 patients to test whether the MSCs (a type of adult stem cell) made from pluripotent stem cells created in the lab is safe and eventually whether it can aid patients facing GVHD, a potentially life threatening consequence of bone marrow/hematopoietic stem cell transplantation. There are 4 key bullet points the company released on the study:

  • “UK regulatory authority MHRA approves Phase 1 trial with Cymerus(TM) MSCs
  • World first clinical trial with allogeneic iPSC-derived product
  • Major milestone for stem cell therapeutics and regenerative medicine
  • Cements Cynata’s global leadership in second generation MSC therapeutics”

Another allogeneic IPSC study, this one in Japan and led by Masayo Takahashi, appears to be on the cusp of beginning using IPSC-derived retinal pigmented epithelial cells (RPEs) to treat macular degeneration. An earlier related autologous clinical study began with one patient receiving autologous IPSC-derived RPEs, but was halted due to regulatory changes in Japan. Also, IPSC-derived RPEs from a different patient were found to have a few mutations, which I’m still unclear as to whether had any significance.

Takahashi’s team just published a couple important papers on the allogeneic therapy reporting encouraging pre-clinical data in non-human primates where there wasn’t rejection. My sense is that their human clinical study is likely to start early in 2017.

I expect between these trials and other coming new ones we could see a half-dozen or so IPSC-based trials in the works by the end of 2017. Exciting times in the pluripotent stem cell-based clinical translation arena.

One question here with Cynata’s approach that first comes to mind relates to the question or autologous versus allogeneic therapies.

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KPBS piece sheds new light on Jim Gass stem cell case, ties to San Diego firms

KPBS reporter David Wagner has an important new piece out today on for-profit investigational stem cell treatments and he focuses to a large extent on a stem cell business in San Diego called Stemedica. If you’ve heard of this company it might be in part because they were involved in the Gordie Howe stem cells for stroke story that got so much buzz.

At a personal level the KPBS story is about the experience of patient Jim Gass, who received a number of non-FDA approved stem cell treatments outside the U.S. and ultimately ended up with a tumor on his spine. 

To be clear, Gass was not directly treated by Stemedica, but Wagner’s article makes the case that there are two relevant links with the stem cell business: a referral of Gass by a Stemedica director to a doctor in Mexico who did a treatment and the use of an MSC product made by Stemedica in that treatment.

Gass was brave enough to go public with his overall stem cell story a few months back. As part of her New York Times piece on Gass earlier this summer, Gina Kolata just briefly mentioned a possible indirect tie to Stemedica:

“I began doing research on the internet,” Mr. Gass said. He was particularly struck by the tale of the former football star and professional golfer John Brodie who had a stroke, received stem cell therapy in Russia and returned to playing golf again.

So Mr. Gass contacted a company, Stemedica, that had been involved with the clinic, and learned about a program in Kazakhstan. When Mr. Gass balked at going there, the Russian clinic referred him to a clinic in Mexico. That was the start of his odyssey.”

In the new piece on Jim Gass’ experience, Wagner provides additional concrete material on this situation in the form of emails to/from Gass, new information in the written part of the article, and via a startling video interview with Stemedica spokesman Dave McGuigan (below).

Wagner writes about how Gass’ treatment took shape:

“Gass traveled to Hospital Angeles in Tijuana, Mexico with the hope of recovering from a debilitating stroke. He received stem cells from Dr. Cesar Amescua based on a referral from Stemedica Cell Technologies, Inc., a San Diego company known for reportedly helping famous former athletes like hockey legend Gordie Howe make “miraculous” recoveries from strokes.”

What is the evidence for that referral that is mentioned?

The email documentation included with the article indicates that Marcie Frank of Stemedica referred Gass to Amescua (see image of part of the email below) in the form of saying, “Please contact Dr. Cesar Amescua”.

jim-gass-stemedica-email

Screenshot of part of Jim Gass email with Stemedica’s Marcie Frank

There are also Jim Gass’ own recollections of his experiences and his photo/video of being injected.

What happened next?

Gass went forward with the treatment, writes Wagner, which involved two kinds of stem cells:

cesar-anescua-jim-gass

Image from KPBS and Jim Gass

“Gass said he followed Stemedica’s referral and got in touch with Dr. Amescua. He said further down the line, he was told that for $30,000, he could receive a round of treatment involving two different types of stem cells.

The first type, Gass said he was told, would be mesenchymal stem cells. He said he was informed that they would be manufactured by Stemedica, and would be injected into a vein in his arm. Stemedica said its mesenchymal stem cells are derived from adult bone marrow.

Gass said he was told that the other type of stem cell would be fetal in origin, and would be injected directly into his cerebrospinal fluid. These fetal neural stem cells, Gass recalled being told, would be procured from Russia not by Stemedica, but by a different company, Global Stem Cell Health (GSCH).”

It’s not at all clear how Gass developed a spinal tumor nor for sure which of the several stem cell treatments he got around the world over the years might have contributed to the tumor.

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What happens next with FDA & stem cells: lower your expectations?

FDA stem cell meetingIn the total the FDA has held 3 days of public meetings on stem cells in the last few weeks ranging from science to policy and hearing from many parties including patients and even stem cell clinics so the big question now is, “what happens next?”

The FDA has 4 draft guidances pertaining to investigational stem cell clinical procedures and these were the subject of the second meeting that last a couple of days. Soon the FDA’s online commenting period related to these issues will close (you can still make comments here, but don’t expect the comment to appear quickly as I submitted mine 4-5 days ago and it’s still not up).

Once that is done, can we expect the FDA to finalize those guidances? And if it does, will the guidances change at all due to the meetings or online comments on the docket? My sense is that the FDA will take at a minimum months to consider the comments at the meeting and those submitted online so it’ll be 2017 most likely before they are even close to taking a next step at all.

I do not expect the guidances to change substantially. As a stem cell biologist, I didn’t hear anything at the meetings in terms of science or data that provided a compelling rationale to change the guidances. The FDA should base its decisions on the biomedical science.

There were a variety of ideas presented at the meeting for changes or new elements to the stem cell clinical arena including a “middle ground” that would get stem cell therapies to patients more quickly, but the trade-off there is that there would be far less data to support the potential safety and effectiveness of those stem cell products. On the whole this would simply put more patients at risk in my view.

Several speakers mentioned starting a registry for stem cell clinics, but I don’t see that as having a major positive impact as there are too many unknowns and complexities. Who would run the registry and pay for it? Who would oversee it (the FDA?) and what would happen if commercial entities were noncompliant with participating in the registry? What about the already existing clinicaltrials.gov?

A big meme at the FDA meeting was the idea of very widespread functional homology of fat stem cells throughout the body via paracrine signaling. Yes, the heterogeneous cells within “fat stem cell” products do make many growth factors that could act in a paracrine manner, but I don’t buy the idea that this makes them homologous to many diverse tissues in the body and I don’t expect the FDA will either.

The future

The FDA could never finalize the guidances, resulting in either the status quo continuing of thorough oversight of the good citizens of the field and little-to-no action on the stem cell clinics. Or even without finalizing the guidances, the FDA could step up its oversight of stem cell clinics, which would be helpful given that there are around 600 of them in the U.S. operating without FDA approval and the FDA has been issuing <=1 warning letter per year lately.

If the guidances remain (finalized or not) and are the basis for the FDA’s current thinking moving forward, then most adipose stem cell clinics should be subject to FDA action given that they are using more than minimally manipulated cells and hence drugs in an unapproved manner and they are almost always using the cells in a non-homologous manner.

Perhaps in the short run the most likely thing is that nothing will happen. As my state’s governor Jerry Brown once famously said to voters, “lower your expectations” and perhaps that can be applied to the FDA on stem cells. However, I’m not going to do it. I’m going to keep my expectations high on this.

Top 10 Google Stem Cell News Stories: Perspectives

What does Google think (if Google does indeed think) are top 10 stem cell news stories right now?

I took a screen shot below.

Here are some thoughts on those stories.

top-stem-cell-headlines

First, lung organoids are neat, but they have been grown before by several groups. Why is that the top story? I’d have to ask Google. Better PR? Still looks interesting and could have real impact for lung disease in the future.

The second story is on the transplantation of allogeneic IPS cells into monkeys without immunosuppression.This is an important finding with clinical impact from Dr. Takahashi’s group.

That third story seems odd to me. Seems like an over the top claim.

The fourth one with its “for the first time” I’m not so sure about and number five seems to be on the same story. I have doubts about that trial given the lack of detail and the potential for harm to patients. It sounds premature.

Then we have cancer stem cell stories at number six and another at number eight.

Number seven and ten both refer to the experience of one patient in the Asterias stem cells for spinal cord injury trial. Number ten’s headline is dubious from a scientific perspective with its “as a result” claiming the stem cells made the man better for sure. I really hope that’s true, but we don’t know yet although more recent data on more patients is encouraging. Controls are needed in the long run to iron things out.

Number nine is about stem cell clinics. It seems to be the only one mentioning the historic FDA stem cell meeting this week.

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.