1st autologous IPS cell clinical trial for vision loss in the US

The NIH announced the launch of the 1st autologous induced pluripotent stem (IPS) cell trial for vision loss in the U.S., focused on macular degeneration.

Kapil Bharti, Ph.D., leader of new IPS cell clinical trial for macular degeneration at the NEI.
Kapil Bharti, Ph.D., leader of new IPS cell clinical trial for macular degeneration at the NEI. Photo is screenshot from NEI YouTube video.

The protocol is based on a solid foundation of pre-clinical animal studies:

“Researchers at the National Eye Institute (NEI) are launching a clinical trial to test the safety of a novel patient-specific stem cell-based therapy to treat geographic atrophy, the advanced “dry” form of age-related macular degeneration (AMD), a leading cause of vision loss among people age 65 and older. The geographic atrophy form of AMD currently has no treatment.

“The protocol, which prevented blindness in animal models, is the first clinical trial in the U.S. to use replacement tissues from patient-derived induced pluripotent stem cells (iPSC),” said Kapil Bharti, Ph.D., a senior investigator and head of the NEI  Ocular and Stem Cell Translational Research Section.”

While work has been slowly ongoing in Japan using IPS cell based RPE products for macular degeneration, there hasn’t been much action elsewhere. This new clinical is the 1st of its kind in the U.S. and an important milestone.

Fig. 4a Schaub, et al JCI 2019
“Fig. 4: DNN segmentation of iPSC-RPE in QBAM images. (a) A deep neural network (DNN-S) was constructed to segment iPSC-RPE cells in absorbance images. To train the DNN, iPSC-RPE monolayers were fluorescently labeled for cell borders (ZO-1) and registered to absorbance images for hand labeling of cell borders. Scale bar = 25 μm.”

Notably, although work in Japan has been focused for years on using allogeneic (donor) IPS cells, the new US study will use the patients’ own IPS cells and hence is autologous, lowering the chance of rejection.

Bharti’s team had a cool JCI paper this year on deep learning related to this project (see Fig. 4a above).

You can watch a video about the new trial below.

The NEI study will begin with a dozen patients and I was glad to see that safety is mentioned as a focus:

“Under the phase I/IIa clinical trial protocol 12 patients with advanced-stage geographic atrophy will receive the iPSC-derived RPE implant in one of their eyes and be closely monitored for a period of at least one year to confirm safety.

A concern with any stem cell-based therapy is its oncogenic potential: the ability for cells to multiply uncontrollably and form tumors. In animal models, the researchers genetically analyzed the iPSC-derived RPE cells and found no mutations linked to potential tumor growth.”

The work in Japan on a few patients has also not reported any tumor growth from IPS cell-based RPE therapies so far.

Overall, I see rigorous stem cell-based approaches as promising for various kinds of vision loss affecting different parts of the eye.

Keep in mind that something very different is going on out there too, which should be distinguished from the news discussed above. Some unproven stem cell clinics and others lacking robust preclinical data have claimed that purported stem cell product injections could help vision loss, but what they’re selling doesn’t clearly work and has in certain cases done great harm.

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11 thoughts on “1st autologous IPS cell clinical trial for vision loss in the US”

  1. Thankfully my left eye is maintaining @ 20/400 but I am totally blind in my right eye. Weiss did BOTH eyes at the SAME TIME!

    Jeff

  2. Hi Paul,
    I did my PhD on the tumorigenicity of cell therapy. I don’t think just checking mutations are enough for preclinical safety data. Do u know what animal transplantation experiments they have?
    Happy to discuss,
    Qin

  3. Hi Paul
    I am glad to see that something is finally happening.
    I made the mistake of jumping the gun and trying one of these unproven clinics and just spent a lot of money for nothing. As well they caused the retina in my right eye to detach totally blinding me in that eye.
    Anyone can contact me if they wish at arisstek@rogers.com
    Tanx

    Jeff

    1. Jeff, I’m so sorry to read that! BELIEVE me… I know what it’s like to be tempted by these stem cell clinics. It’s a miracle that I was able to avoid them. But I would love to see discussions on whether the types of treatments talked about in this (and other similar) articles could eventually cure your issue too.

  4. Hi, Paul:

    Here’s the fundamental problem with iPSC-based treatments like this one. Tissue cell biology 101: “human tissues turnover.” Essentially all mature endothelial, epidermal, and epithelial cells, in particular, have finite half-lives, which are much shorter than the human lifespan. They are produced by tissue stem cell divisions, mature, function for a relatively short time, die, and then have to be replaced by the resident continuously asymmetrically self-renewing stem cells for the tissue. No replacement tissue stem cells in the therapy, no stable tissue repair. Since neither unethical human embryonic stem cells nor their ethical cousins, iPSCs, can provide this asymmetric self-renewal function, they themselves also cannot provide sustained tissue repair. IPSC therapies try to avoid the problem of the iPSCs being tumorigenic by producing and administering instead their non-dividing differentiated derivatives. But these cells have no cell renewing capability; and they also have the genetic and epigenetic defects of their iPSC parents, which may pose other ignored problems, too. As some have been suggesting for two decades now, we need to invest more research dollars into understanding how to produce postnatal tissue stem cells for development of therapies for postnatal tissues, instead of just bumbling ahead non-scientifically, with known gaping biological flaws, hoping that something magical will occur.

    James at Asymmetrex

    1. Good courageous discussion, re renewing capacity lacking, just want to note that isoptope studies have shown that other than hippocampal or post-TBI, brain-parenchymal neurons in adults are from birth. I.e. some non-dividing cells have quite a lifetime, and remain good grafting candidates, (while admitting that so far, clinical success has been limited)

    1. This is just the 1st such trial in the US. Of course, work started in Japan years ago. But it’s also notable that this new US study is autologous and the work in Japan is allogeneic. The more solid studies going on around the world on macular degeneration, the more hope for patients one will succeed.

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