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 in which the authors attribute these patients’ experiences to a withdrawn “trial”, NCT02024269, which lists Bioheart (now known as US Stem Cell, Inc.) as the sponsor. I put “trial” in quotes because it was withdrawn and also because as best as I can tell this wasn’t a traditional FDA-approved trial of the kind normally based on pre-clinical data and an IND.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

Encouraging New Paper on ACT Stem Cell-Based Trial for Macular Degeneration

The stem cell biotech Advanced Cell Technology (ACT) reported new, positive data in a paper in Lancet from their clinical trials using retinal pigmented epithelial cells (RPEs) made from human embryonic stem cells (hESC) for treatment of different forms of macular degeneration (MD).

The paper was entitled “Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt’s macular dystrophy: follow-up of two open-label phase 1/2 studies” with first author Steven D. Schwartz and senior author Robert Lanza, CSO of ACT.

These two trials (one each for Stargardt’s MD and age-related MD (AMD) with 9 treated patients each) are combined prospective phase 1/2 studies. The primary goal of these trials is to assess drug safety. Importantly so far no major adverse outcomes were reported, but some adverse side effects appeared related to the procedure itself and to immunosuppression so those must be kept in mind. As to the latter, in theory an autologous induced pluripotent stem cell (IPSC)-based therapy could be superior in terms of likely not needing immunosupression, but there may be practical advantages to an hESC-based therapy in other ways (e.g. lower cost).

A potential major bonus here in the ACT report today is that despite the fact that the trial used relatively low doses of cells and despite the primary measure here being safety, ACT reported in this publication that a substantial number of the patients also had measurable improvements in their vision:

Vision-related quality-of-life measures increased for general and peripheral vision, and near and distance activities, improving by 16–25 points 3–12 months after transplantation in patients with atrophic age-related macular degeneration and 8–20 points in patients with Stargardt’s macular dystrophy.

This is a very positive, even if somewhat surprising development in terms of potential efficacy. The main cause of vision impairment in MD is not thought to be loss of RPEs, but rather photoreceptor cells. So how could transplanted RPEs (and relatively low cellular doses for the most part at that) potentially improve vision? The working theory seems to be that the RPEs might help remaining photoreceptors stay alive, healthier, and perhaps more properly functional.

ACT FIgure 1

I thought it was notable that 72% of the transplant recipients had measurable increases in subretinal pigmentation and pigmentation gradually increased over time, indicative of a high-rate of stable engraftment of the RPEs (see image above from Figure 1).

The authors summarized their interpretation of their results in this way:

Our study provides the first evidence of the medium-term to long-term safety, survival, and possible biological activity of pluripotent stem cell progeny after transplantation in people with any disease. The results suggest that human-embryonic-stem-cell-derived cells could provide a potentially safe new source of cells for the treatment of various medical disorders that require tissue repair or replacement.

I’ll be very curious to see the future results as ACT likely begins to treat patients with higher doses of cells and patients with relatively earlier (potential more treatable) stages of MD.

In the wider scheme of things, ACT’s results are also encouraging for other stem cell biotechs and other similar kinds of studies. For example, it will be interesting to see how the IPSC-based RPE clinical study in Japan for MD proceeds and how the BioTime subsidiaries (1) Asterias’ hESC-based trial for spinal cord injury and (2) Cell Cure’s hESC-based trial for AMD proceed. There can perhaps be greater hope of safety for these other vision-related pluripotent stem cell-based trials as well now and also for other studies such as ViaCyte’s hESC-based trial for Diabetes, which may start very soon.

Still, it’s relatively early days and these kinds of endeavors are risky marathons rather than sprints, so quite a lot of caution is in order.

Disclosure. The author has a small, long-term stock position in ACT. This post is not intended to be financial or health advice. Consult your financial advisor and doctor (not blogs) for making those kinds of important decisions.