Macular degeneration: 'I've been given my sight back'

http://www.bbc.com/news/health-43458365

by obeone • 8 years ago

295 53 8 years ago

bbc.com

pmarreck2• 8 years ago

Cells from a human embryo

Are they sure? They can now harvest stem cells from regular tissue and blood, as I understand it

matte_black• 8 years ago

Yea but they probably need to be young versions of your stem cells.

iPS stem cells from old cells will still be fraught with DNA damage and can be cancerous.

maxerickson• 8 years ago

It's the BBC. They make mistakes, but it is entirely reasonable to start from the assumption that they have not made such a big mistake.

Anyway, here's a publication about the study that makes it pretty clear that they got it right (abstract only, paywall):

https://www.nature.com/articles/nbt.4114

(I found the study by assuming a page like http://www.thelondonproject.org/ would exist and then following the link provided)

ars2• 8 years ago

http://sci-hub.tw/10.1038/nbt.4114

Brakenshire3• 8 years ago

Are they sure? They can now harvest stem cells from regular tissue and blood, as I understand it

There are adult stem cells which are differentiated or partly differentiated to particular systems, eyes, skin, blood etc, and there are induced pluripotent stem cells, where chemical or viral factors have been used to 'wind back the clock' for adult, differentiated cells back to completely non-differentiated (pluripotent) stem cells, equivalent to embryonic stem cells.

In the long run, it seems that embryonic stem cells won't be needed, but for the moment induced pluripotent cells are not 100% understood, everywhere apart from Japan clinical researchers are wary of using them in human trials, because they are not completely certain a particular preparation doesn't have abnormalities. Embryonic stem cells for the moment are the gold standard, and some work is needed to iron out the technology to standardize and check the process for inducing pluripotency.

But in principle any cure proven with embryonic stem cells could be 'ported' over to induced pluripotent stem cells once the iPSC process is standardized, it's just a question of whether you want to pursue these two research paths in parallel, or wait for the iPSC problems to be ironed out before even starting the process of running human trials.

hcknwscommenter• 8 years ago

Very well put. I would add that it could take decades to "iron out" the issues with iPSCs. It could also never actually happen. For example, the iPSC generation process induces oncogenic properties in the cells ( https://www.ncbi.nlm.nih.gov/pubmed/22998387 ). It could be that in the next few decades, iPSCs just turn out to be a lot less safe than embryonic stem cells. Considering the hundreds of millions of dollars it could take to move stem cell therapies like this through the validation and regulatory approval process, it would be foolish to handicap the process by using "unproven" iPSCs in favor of "gold standard" embryonic stem cells.

pmarreck2• 8 years ago

This high-quality comment and its followup (so far) are why I come to HN. Thanks!

mosselman• 8 years ago

“He was one of two patients given pioneering stem" I find the tiny test groups in medical ‘research’ so strange.

sp332• 8 years ago

It's a test to see if they should bother moving forward. You don't want to gear up a big study just to find out that the treatment gives everyone cancer (which is a concern mentioned in the article) or that it doesn't work at all. You do a pilot study to see if there is potential before you waste a lot of work and maybe hurt people.

Anyway if the effect size is big enough, you don't need a really large study to get statistical significance. I mean, what are the odds of macular degeneration reversing by chance?

sametmax• 8 years ago

We do the same in web ergonomics. Testing you Ui on 3 people is enough to see the biggest flaws of the tool and engaging in more expenses. See the excellent book "don't make me think" for a quick and efficient write up on the topuc.

bluGill• 8 years ago

unfortunately that is all we have. There is nobody on earth with your exact genetic makeup (even identical twins, though then the random mutation is small enough to ignore: consider it an exception). As a result nothing exactly will behave correctly for you. A drug that causes death in 99% of those it is tried on might be the one you need, but because it is so deadly trials will ensure it never makes it to market.

ainiriand• 8 years ago

It is normal in phase 1 trials involving complicated surgeries.

Brakenshire3• 8 years ago

This is a phase 1 trial (usually just undertaken to check safety before larger trials are done to test efficacy and dose), so it seems all the more amazing that such a big improvement was seen.

epmaybe2• 8 years ago

From the article, 29- and 21- letters improvement in visual acuity. I believe this means at least 4-6 rows improvement from the chart you read off of.

Think about that for a second. Nearly blind, or actually blind, to being able to read again.

I'm seriously debating specializing in ophthalmology, and sub-specializing in retina surgery just became an even more appealing career plan for me.

philbarr2• 8 years ago

helping people be able to see again? sounds like a definition of "job satisfaction"

jorgen123• 8 years ago

I would applaud that choice.

I had a retinal tear 4 weeks ago and then then retina detached and started sagging in front of my lens, blocking half of my field of view. Seriously scary, especially since my mother has lost most of her vision after a similar problem.

I got a pneumatic retinopexy a couple of days later. Amazingly, it only took about 30 minutes in a (nice) back-room of the retina clinic with local anesthesia, and the retina re-attached itself in the course of the next few days. Now I am just waiting for the gas bubble to dissolve while my vision is getting better each day.

gwern• 8 years ago

Strictly speaking, it's a big improvement because you're hearing about a phase 1 trial, and predictably so - not surprising at all.

Phase 1 trials typically get little publicity unless they either kill someone or turn in a statistically-significant improvement. (A phase 1 trial in which the controls do exactly as well as the experimentals and no side-effects are observed, which is highly likely for even excellent treatments because of the tiny sample size, will very rarely be written up because it's boring.) And because their sample sizes are always tiny, any statistically-significant improvement will always be an extremely large effect size. If the effect hadn't been improbably large, you would almost certainly not be reading about it now on HN.

And because of this selection bias, the effects you hear about tend to be massively overestimated. This is one of Andrew Gelman's points: the 'statistical significance filter' massively inflates effect sizes, a type M error, which then subsequently regress to the mean of the true smaller effect. This is why you're not supposed to take Phase I trials as meaningful estimates of the effect size, why statisticians emphasize they're supposed to be about safety, and why you don't do power analysis based on the observed results (either post hoc or for designing the next big ones). This is also part of why you hear about so many amazing pilot experiments in animals or humans but then the big followup trials are much more modest or nulls.

Brakenshire3• 8 years ago

Interesting point. I was thinking about it in terms of dose, usually phase 1 trials seem to have significantly lower doses, to feel out any issues with safety. But perhaps that doesn't apply in this case, and you are left with the issues you mention about statistical significance, selection bias and regression to the mean.

reasonattlm• 8 years ago

Most stem cell therapies produce benefits through the signaling of the transplanted cells, near all of which die off rather than integrate. This is an example of an approach that goes beyond that, providing a set of more organized cells in a thin tissue segment that looks more like the native tissue. When this was done for the heart, 10% of cells survived (this is a large number in the scope of stem cell therapies).

So it is interesting to speculate on the degree to which the benefits here are signaling versus cell integration. Clearly the big difference between past attempts is that a tissue-like set of organized cells are delivered rather than just free-floating unorganized cells.

chapill• 8 years ago

Cells from a human embryo were grown into a patch that was delicately inserted into the back of the eye.

I assume the baby didn't survive the process since there's no mention of that.

jackhack• 8 years ago

This is important because, for some, the moral dilemma would preclude this treatment.

warent• 8 years ago

In one sense, the cells did survive as part of the 86 year old lifeform. It's a ship of Theseus

philbarr2• 8 years ago

It's not a baby, it's an embryo. Lots of embryos don't survive for lots of reasons.

gottebp• 8 years ago

It's a philosophical dilemma that demands rigour. When does a human person begin? If a few cells cannot be a person, well, adults are only bigger clumps of cells. What is the threshold? If personhood begins when the cells are independently viable, well, most infants are not independently viable and some elderly aren't either. What is the threshold? By contrast: The moment when it all begins and the DNA is first unique, and the potentiality for an adult is present is very simple and philosophically elegant. If personhood comes later, such as implantation, birth, 7th birthday, etc. it is difficult to give a basis in the philosophical sense. Many philosophers have struggled with this and it's no simple thing.

GlennS• 8 years ago

It may be worth knowing that you don't have to kill an embryo each time. Once you've harvested a stem cell line, you can use it repeatedly.

random_ind_dude• 8 years ago

baby

If, at some point in the future, scientists figure out a way to coax normal cells to become totipotent, will you consider amputation as murder?

nsxwolf• 8 years ago

No, because you'd have to first take the step of inducing totipotency in the amputated cells?

maroonblazer• 8 years ago

I'd love to know if similar work is being done for loss of hearing/deafness. Is there an auditory equivalent to retinal pigment epithelium that nourishes the hair cell stereocilia?

robohoe• 8 years ago

I would love to see if there are any updates/trials going on in regards to hearing/deafness. Suffering from Tinnitus and hearing loss is not pretty.

todd102030• 8 years ago

I'm by no means experienced in this field, but wouldn't cochlear implants count to some extent? I know those sidestep the hearing loss rather than fixing it directly, but the end result is essentially the same. My mom has dealt with hearing loss since her early years of childhood, and peaking in total hearing loss about 15 years ago. Just a year or two later, she was included in a study and was able to get a cochlear implant for free. Not too long after, she was lucky enough to be offered a second one at no charge (the benefits of being a beta tester), and to this date, she's still being given new speech processors that constantly improve the quality of sound as well as adding new features. It honestly blows me away with what they've done already with hearing, and I won't be surprised if in 10-15 years, those implants surpass a normal human's capabilities, and people who still have perfectly working ears start getting them.

DoreenMichele• 8 years ago

Alternative remedy groups recommend magnesium supplements to treat tinnitus. I know at least one person whose tinnitus improved and became more bearable after improving their magnesium status. I rapidly get noise sensitive when I become magnesium deficient due to fever or vomiting and it rapidly resolves with consuming magnesium rich foods.

If you are magnesium deficient, you may also need calcium, vitamin D and vitamin K to fully resolve the issue.

snegu• 8 years ago

This lab at Stanford is working on some similar things (there are also other research centers I can't recall right now): https://hearinglosscure.stanford.edu/

I'm watching them like a hawk hoping that some day my 2 year old son might benefit from their work.

etskinner• 8 years ago

Both patients in the trial had "wet" age-related macular degeneration. This form of the disease is caused by abnormal blood vessels growing through the retinal pigment epithelium and damaging the macula. Dry age-related macular degeneration is more common and caused by the retinal pigment epithelium breaking down.

If this is a viable treatment method, it would help only the minority of macular degeration patients.

pinum• 8 years ago

It is hoped the patch will be able to treat both forms of the disease.

AnimalMuppet• 8 years ago

If I understand correctly, "wet" progresses much more rapidly than "dry". You're much more likely to unexpectedly lose your sight to "wet" (as opposed to just slowly having your sight deteriorate).

Feel free to correct if I'm wrong. I'm not an expert. This is just what I've gathered from having two family members with it.

tombert• 8 years ago

About a year and a half ago, my wife was showing symptoms of early-onset macular degeneration, and it led to a rabbit hole of me searching for treatments, and I remember the earlier stages of this being discussed.

While it turned out that my wife's issue was (fortunately) something less severe, it still makes me happy to see that this treatment has had some success.

abledon• 8 years ago

I'm really curious to see what the statistics of early-onset macular degeneration will be in 30-40 years, when a large portion of the population will have been looking at screens 10+ hours a day, for 30+ years. I suspect humans current eye-usage habits will affect the numbers.

results in this area of the field can't come fast enough!

jtl999• 8 years ago

What's the latest on optic nerve regeneration with stem cells?

logronoide• 8 years ago

My mother had macular degeneration. She lost almost all vision in a couple of years. She was a very active women all her life, a business woman when women had to ask permission to her husband to open a bank account. It was devasting for such an independent person. She was deeply depressed and being in her early seventies her health deteriorated quickly, finally dying.

If researchers find a solution it will improve the quality of life of millions elder people.

bennyg2• 8 years ago

I have had 4 retinal detachment surgeries on my left eye, with the last rendering it blind.

I had one retinal detachment surgery and a subsequent cataract surgery (since vitrectomy almost always results in a cataract) on my right eye. It's fairly stable but my vision is not great.

I'm hoping for stem cell therapy sometime in my life to help repair areas of my right eye that are no longer great (retinoschisis and general rod/cone dystrophy) and to make sure I'm seeing well into my later years of life.

davidw• 8 years ago

Wow, that's pretty cool. One of the things I worked on a couple companies back was this: https://www.centervue.com/products/compass/ which is a system used to measure how much people are losing their vision from things like macular degeneration.

Macular degeneration: 'I've been given my sight back'

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