NEJM paper links 3 blinded patients to publicly-traded stem cell clinic

Do 3 blinded stem cell clinic patients with major or complete vision loss constitute a significant adverse outcome?

I would say so and a new paper details how this happened apparently at a particular publically-traded South Florida stem cell clinic business.

You can see the damaged retinas of one such patient below in an image from a new NEJM paper reporting the severe adverse outcomes. The red areas are hemorrhaging with other substantial damage to the retina as well.

How did this all happen?

stem cells eyes

Kuriyan, et al. 2017 NEJM Figure 2A

Last year the story began to break of multiple patients alleging they had been blinded by different businesses in South Florida. Dr. Thomas Albini presented on some information on this at the FDA meeting last fall, but things weren’t entirely clear. Back then there were also indications of lawsuits by patients related to alleged vision loss due to experimental stem cell offerings against various parties involved.

Now we have more details on some of the cases in this new NEJM article (Kuriyan, et al.) in which the authors attribute these patients’ experiences to a withdrawn “trial”, NCT02024269, which lists Bioheart (now known as US Stem Cell, Inc.) as the sponsor. I put “trial” in quotes because it was withdrawn and also because as best as I can tell this wasn’t a traditional FDA-approved trial of the kind normally based on pre-clinical data and an IND. US Stem Cell, Inc. is a publicly-traded company ($USRM) and its stock has been all over the place this year. I’m not aware of US Stem Cell having FDA approval for what it is doing.

The NEJM article oddly does not mention Bioheart or US Stem Cell, Inc. by name as the place where the patients were given the stem cells, but the authors do clearly link them together and other information further supports this connection. Continue reading

How Scott Gottlieb may transform the FDA’s approach to stem cells

The Trump FDA commissioner nominee Dr. Scott Gottlieb Dr. Scott Gottliebcould dramatically alter how the agency regulates investigational stem cell therapies. How might such changes unfold? There are potential upsides and downsides to  the seismic shift that could be in the offing.

Gottlieb has written in the past about his perception of FDA over-regulation of stem cells such as in this piece in the WSJ. There he made a number of assertions that signal his view at least back then that when it comes to regulation of stem cells by the FDA, less is more.

More recently, a speech he gave at an ISSCR meeting in Berkeley last year is much more balanced in tone than the 2012 WSJ piece. This quote from the Berkeley talk, for example, is balanced and emphasizes standards:

“Expediting the development of these novel and transformative technologies like gene- and cell-based therapies doesn’t necessarily mean lowering the standard for approval, as I believe other countries have done. But it does mean having a framework that’s crafted to deal with the unique hypothetical risks that these products pose.”

Still that WSJ article is concerning.

For instance, he and his co-author Coleen Klasmeier, both former employees of the FDA, strongly criticized a federal court ruling in 2012 that the FDA could regulate laboratory-proliferated stem cells as a biological drug. Oddly, much of the basis for their criticism was far broader than the reality of the court ruling. They suggested, for instance, that the ruling opened a veritable Pandora’s box of FDA over-reach potential that extended to all autologous uses of stem cells (lab-grown or not) and beyond, but that was not the case as the ruling was focused on lab-grown stem cells. Even so they made largely unsupported generalizations such as the following:

“If the FDA’s victory is upheld on appeal, then conceivably nothing done as part of clinical practice is beyond the agency’s reach.”

In the intervening years since the 2012 court ruling and the WSJ article, we have seen that the sky hasn’t fallen from the FDA having obtained the defined authority to regulate lab-expanded stem cells as drugs. In fact, oddly enough if anything the more time that has passed, the less inclined FDA’s CBER biologics branch that oversees stem cells has been to take action on stem cell biologics. It’s hard to view the FDA issuing less than one warning letter per year to stem cell clinics even as there are upwards of 600 of these clinics as a form of overreach.

From a scientific and medical perspective, there are good reasons to regulate lab-grown stem cells as drugs. The cells are known to change their differentiation properties, accumulate mutations and epigenetic changes, and undergo other significant alterations in the dish in the lab. There is also, perhaps more directly related to the FDA’s mandate on biologics, substantial potential for contamination of cells in a lab during proliferation.

Since 2012, another big change has been the explosion of adipose stem cell clinics onto the scene, which use more than minimally manipulated liposuctioned material to make a biological drug product via enzymatic and other steps. However, the clinics argue their products aren’t drugs and they generally do not have any FDA approval to market stem cells. Nonetheless such offerings are being sold at hundreds of clinics around the country. How would a newly minted FDA commish Gottlieb view these clinics? Through the same lens as the autologous, homologous bone marrow-based approaches? What about the clinics using bone marrow and amniotic cells in non-homologous manners that make such products drugs? Continue reading

Q&A video with Paul Episode 2: stem cell & CRISPR questions answered

This is the second in a series of videos I’m doing where I answer questions about the stem cell field. You can see the Episode 1 video here.

Today I tackle more questions on the stem cell field. If you have more stem cell questions, let me know and I’ll try to answer them next time.

One reader asked me about stem cells for stroke and about one company, Athersys, in particular, but I haven’t had time to tackle that one in such a way as to do it justice so stay tuned on that good question.

I realized after the fact that regarding stem cell epigenetics I should have said broadly that this is a process of regulation of gene expression.

Poll: How will Trump’s FDA handle stem cells?

Paper on 1st use of CRISPR in normal human embryos: problems remain

The first report of the use of CRISPR gene editing in normal human embryos was published today as a short paper from a team in China. There have been rumors for over a year that more CRISPR human embryo papers were coming including some using normal embryos. Here’s one and we can now expect more even as there remain scientific and ethical discussions about this kind of work.

CRISPR human embryo Tang et al

Figure 1b, Tang, et al. CRISPR of 3PN embryos.

You can read the actual paper Tang, et al. here, published in the journal Molecular Genetics & Genomics. This work was published by Jianqiao Liu’s lab. They attempted editing in both abnormal (3PN)  and normal human embryos. Figure 1b from the paper of CRISPR’d nonviable embryos, is shown above.

Some proper gene editing was reportedly evident after injection of CRISPR in normal human zygotes. Further, the efficiency of the genetic modification of the CRISPR’d embryos was higher in the context of using healthy embryos than in previous reports that used nonviable embryos and in the nonviable embryos used in this same study.

But major problems remained such as incorrect editing (making of a disruptive Indel rather than a correction) and quite a bit of mosaicism. While they did not detect off-target effects at a handful of specific predicted possible off-target sites or by some WGS, such sites could still exist. Continue reading