August 5, 2020

The Niche

Knoepfler lab stem cell blog

Perspectives on new stem cells for vision loss paper

stem cells for vision loss
Kashani, et al. Science Translational Medicine, 2018, Figure 2

Do stem cells for vision loss offer real hope?

I believe so, but it’s a long road and must be done right.

A new paper in this area generated some buzz on top of an earlier recent pub (mentioned in this post) just a week or so ago about the potential of stem cells for vision loss.

The new paper is entitled, “A bioengineered retinal pigment epithelial monolayer for advanced, dry age-related macular degeneration” and is Kashani, et al.

They generated special eye cells called retinal pigmented epithelial cells or RPE from embryonic stem cells and a bio-device with the RPEs was implanted in 4 patients. RPE don’t directly function in vision (sensing light), but can help to keep other cells in the eye happier and healthier, including importantly photoreceptors.

I’m cautiously upbeat about this work for a number of reasons, but mainly because of the safety profiles and not because of any possible hints at efficacy reported.
For years, there was concern that using human pluripotent stem cells as the basis for therapies including for vision loss, even if the stem cells themselves were only used to generate differentiated eye cells for subsequent transplant and were not themselves directly part of the treatment, might be too dangerous as they have the potential to form benign but destructive tumors called teratomas. This new work along with other studies including using IPS cells point to a reassuring overall inherent safety profile so far. While there have been some adverse events, they appear to relate specifically to the procedures involved rather than the cells themselves and importantly there haven’t been tumors so far.
The major caveat with this and other similar work is that they are small, open-label studies without control groups, meaning that they do not have the power to determine if any observed potential small signs of efficacy such as hints at improved vision or halting of loss of vision are real and due to the cell therapy. So the jury is still out on stem cells for vision loss.
The clinical work led by Masayo Takahashi is still of great interest as well and is focused on using IPS cell-derived RPEs too. They have not observed tumors, but there have been challenges there that have slowed things down somewhat including the report in January of a membrane forming after introduction of stem cell product.
Another pluripotent stem cell-based effort at stem cells for macular degeneration ongoing for many years is the work led by Robert Lanza of Astellas, work that began in the company ACT and then renamed Ocata. It’s been very quiet on this front since Astellas acquired this research program. When I last communicated with Bob in May 2017, he indicated the work was very much ongoing still, but I’m hoping somehow we’ll all get another update soon.
Why has this all been so hard and time-consuming?
Beyond the challenges mentioned earlier with potential risks associated with pluripotent stem cell-based approaches that necessitate extra caution and take a lot of time, more broadly it is very challenging to translate any kind of stem cell therapy from the bench to the bedside in a responsible way that doesn’t put too much risk or financial burden on patients, and has a solid chance of efficacy. This is demanding, extremely complex research thatI’d say is harder than rocket science. Also, we have to be very careful to avoid hype.
You can see just how badly rushing unproven stem cells for eye problems at the far other end of the spectrum where unproven, for-profit stem cell clinics have sold offerings to patients, reportedly leading to retinal detachment and loss of vision (here and here).
In the long run, I think that stem cells for vision will succeed and they are going to be the basis for proven, safe therapies, but we need to do it right in terms of the research.
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