Tag Archives: takahashi

My fun trip to Casey Eye Institute this week, and the results…

So on Wednesday, I sat in the waiting room of Casey Eye Institute again, heart pounding, hands numb with terror where my fingers clutched at the wooden arms of the chair. (And if you think *that* sounds bad, then you should have seen me every time I had to go there four years ago!) I was surrounded by little old ladies in wheelchairs and inching along on walkers, their faces full of stubbornness and determination, with the flashing eyes and set lips of survivors. As usual, there were a couple of children, too. I tried to never look at the children, sitting quietly by their mothers, their faces hidden behind thick glasses, their faces filled with the weary patience of eight or nine year olds who have spent too much of their young lives in doctor’s offices and waiting rooms. There’s a lot more of this type of description in my memoir, but you know, I think we’ll stop there for the purposes of a blog post.

The point is, I went to Casey again, which I have to do twice a year. As usual, I would rather have been chased off a cliff by rabid wolves. But I sat in the chair while the retinal scanner went up and down my eyes; I sat in another chair while the cute and chirpy assistant stuck a dubious-looking metal thing meant to measure glaucoma right up against my eyeball, and I sat in the really fancy chair as I waited for Dr. Lauer to come in and interpret it all. (Hint: meditation mp3’s don’t really help in this situation.) And the news was…

(drumroll)

IT’S ALL GOOD!

Okay, maybe it’s not exactly *good*, but my vision is stable. There’s nothing new going on (which would mean new and bad; definitely not new and good.) The first doctor who looked at my retinas through that horrible bright slit lamp thingy was amazed that I hadn’t needed a new Lucentis injection since 2011. This really isn’t normal, and nobody seems to know why the first injections have held up so long. Of course, nobody ever exactly identified the original disease, either. 😛 So I was set free that day to skip out into the sunshine of the wide world outside OHSU, as people looked at me and wondered if I’d escaped from the psych ward.

But it did make me think about a few things.

Yes, this is good news. But there’s never any guarantee. I really do live one day at a time. And I know how lucky I am compared to a lot of people. Most younger patients are not helped by anti-VEGF drugs at all. It makes me a very impatient patient when I think about all the glowing news in the past few days,. Very little of the gushing is supported by fact. The much-ballyhooed treatment at Moorfields isn’t just in the first experimental stages. It’s also dangerous, invasive, scarring, risky to the survival of the retina, and extremely expensive. Why is there so much over-the-top excitement about it?? It’s exactly like the wet AMD treatment in Japan earlier this year, the one based on IPSC’s rushed to the clinic dangerously fast. The study was abruptly stopped, and nobody ever got a straight answer as to why. Other scientists have skirted the issue, showing a lot of professional courtesy in not confronting Dr. Takahashi, I’m sure, but not much regard for the rights of patients.

It’s hard to wait. But it’s good to know that we are waiting for something that works. That doesn’t set aside the issue of what may or may not happen in Phase II. But it does acknowledge the fact that we know that for the people in the Ocata study, the treatment to date has worked. I, for one, am over the excited gushing surrounding experimental treatments that haven’t even begun to do that much. Because we, the patients, deserve better than this. Everyone going through their own personal hell at Casey on Wednesday deserves better. I believe that we will get it. I have learned to wait, God only knows how. I haven’t been to any mountaintop, but I have seen a glimpse of it. We will get there, and we will do it together. So I say to everyone,… have faith, and hold on!

My Amazing Powers of Predicting Disaster: Failure of the Takahashi Trials

!!!!!!
Ahem.

Well, the Japanese Takahashi trials with the induced pluripotent stem cells are turning out to be a dangerous failure. Read all about it here. Just as SOMEBODY predicted. Hmm… I can’t imagine who…

Anyway. The trials were stopped because, in the words of New Scientist: “ genetic mutations were discovered in the cells of the second trial participant. One of the mutations may carry a remote risk of cancer.” (Remote… oh really? This is the same publication that has carried gushing fan news about the IPSC trials since Day One. Of course, so have all the rest… but still, I wouldn’t trust a disclaimer like that as far as I could throw it.)

Hmm… .WHO predicted this failure last year? WHO posted these predictions multiple times all over the web, including Paul Knoepfler’s blog and investorstemcell.com? WHO said it was way too soon to rush into the clinical setting when there hadn’t been even a tenth of the number of animal studies that should have happened first? WHO held fast to this prediction, even when nobody agreed with her and nobody wanted to hear about it?

Could it be… ME??

Hint: the answer is yes.

I’m NOT posting the link to Randy Travis singing “I Told You So” again. This is actually beyond even what I dared to predict last fall for the IPSC trials. That’s it. There HAS to be a way to turn this amazing psychic power to predict disaster into something valuable… (hmmm)

Anise: (poring over a crystal ball while clients wait impatiently) I can tell you all the Powerball combinations that aren’t going to win.

Clients: Isn’t there a faster way?

Anise: No. But I can give you all 174 million losing number combinations, and you just have to go through them– wait– where are you going??

The point is that I knew the IPSC trials wouldn’t work. They were rushed to the clinic crazy fast because it was a chance for Japan and Riken to get the first clinical trial of IPSC’s underway. This represented a chance to save face after the STAP cell disaster last year. To tell you the truth, it’s not rocket science and is very easy to piece together. However, this kind of outcome is what I hoped wouldn’t happen. But it was always a possibility. I posted long, long threads about it in the past, and we really don’t need to go into all of it again here… suffice it to say that there are good reasons to have a lot more animal trials before jumping immediately and dangerously fast into clinical trials.

You know… this sounds horrible, but the failure of these trials will ultimately help Ocata a lot. One by one, the inferior and not-ready-for-prime time stem cell treatments are falling. Ocata’s treatment for AMD is the only one that continues to advance through all trials with flying colors. And since this is treatment I would need… well, I think I have the cred to say it!!

Also, it would have been good for that article to get Ocata’s name right. 😛 But you know… there’s good and bad in everything.

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UC-Davis Stem Cell Ethics Conference: Part Six, The Amazing Paul Knoepfler

Hey, all! Yep, today our story continues. When we left off at the end of Part 5, UC-Davis scientist and stem cell blogger extraordinaire, Paul Knoepfler, was about to take the stand to speak… and here he is. There’s also a teaser at the end for a BIG surprise tomorrow, in Part Seven…
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“The FDA’s mission is to assist safety and efficacy and speed innovations,” Paul Knoepfler said in a soft voice. “The issue is getting the two to mix. Believe me, I do realize that a lot of people see this as an issue. But the thing is, no other regulatory body oversees stem cell medications in the U.S. And in the past, various drug mistakes have hurt or killed people. There’s no way around that. Thalidomide is a good example.”

Oh, please, please don’t show any slides of deformed babies, I silently prayed.

Whether it was because he’d read my mind or not, none of those were shown. I knew what had happened in the late 1950’s with thalidomide, a drug originally used as a mild sedative and sleeping pill. It was also given to pregnant women to lessen morning sickness, with tragic, unforgivable results. But what I hadn’t known was that the FDA had not approved the drug in the US, despite considerable business pressures at the time. Thalidomide had been marketed and sold in the rest of the world, starting in Germany. It was one of the most widely prescribed drugs of any kind in that era. If I hadn’t already been listening intently—which I was, of course, because this was Paul Knoepfler—then that was a fact that would have made me sit up and pay attention.
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UC-Davis Stem Cell Ethics Conference: Part Five

Hey all,

So… we’re done with the raw notes for now, and we’re back to the writing! Believe me, you do NOT want to miss the info in today’s installment. If you’ve ever wondered whether or not you should keep your investments in a certain biotech company, for instance… the answer’s here. Enjoy!
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PART FIVE.
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More thoughts about Japanese stem cell trials right now…

I was working on the section of my book that deals with iPSC stem cell trials in Japan– a little bit about the history, Yamanaka’s discovery of iPSC cells in 2006, and how it all got to where we are now. There’s a lot of material about where we actually are at this point, too. Reading over what’s there so far, it’s kind of hard to avoid the conclusion that I’m sounding pretty negative about the Japanese research. It’s not that I want to take a negative attitude about it– I’d much rather see that research succeed– but they’re moving so fast, and I just can’t get on the rah-rah bandwagon. Here’s a good example of what I mean.

Over the past couple of years, Paul Knoepfler has posted a lot of concerns and critical thoughts about the process of getting iPS cells to clinical trials, and he’s used some pretty strong language. For example, here’s part of what he posted in October 2012:

Are iPS cells being rushed to the clinic or has their time come?
Just the title alone kind of tells us what his thoughts might be, but there’s much more. Here’s a very relevant quote:

The iPS cell field has run fast and furious over the past 6 years reaching a big milestone surprisingly quickly on Monday with Shinya Yamanaka winning the Nobel Prize.

But is the field going too fast?

In August I argued that iPS cells are not quite ready for primetime (i.e. clinical trial studies).

Now in October I mostly feel the same way.

But reportedly, some iPS cell researchers are working to start clinical studies wherein iPS cells would be transplanted into human patients as early as next year in Japan.

This is both exciting, but also potentially very risky if not flirting with disaster.

It would be tragic if the excitement and creativity exploding from iPS cells became diminished in the future by a rush to the clinic that harmed patients.

Pretty strong words. In fact, let’s look back at the August 2012 blog post that Paul referenced:

iPS cells not quite ready for primetime?

I like and support the idea of iPS cell banks (as discussed by Yamanaka). However, I do not believe the field has advanced far to support clinical use of iPS cells in the near future.

I realize that clinical use may nonetheless be on the horizon just a few years out in certain countries such as Japan, but in my opinion iPS cells are “not ready for primetime”, meaning not ready for clinical use. Not yet.

I also realize that some people in the stem cell field are going to be mad at me for saying this, but I believe it is true. People don’t read this blog to get sugar-coated, politically correct statements, right?

Are we ready to start using iPS cells in patients in the near future? Say in just a couple years?

Are they ready for primetime?

I think the answer is clearly “no”.

Guess what? This blog post was written in August 2012; Takahashi and company performed the first human transplant in September 2014. This means that the EXACT situation that Paul warned about, the EXACT one that he said absolutely should not happen, is EXACTLY the one that happened. (!!!) (feel free to add more exclamation points.)

But that’s far from all he had to say. Now, let’s fast forward to April 2013, only a year and a half ago:

As iPS cell studies in humans approach, accessible relevant pre-clinical data remains minimal

This dealt with Japanese scientist Takahashi and her attempts to get the first-ever human trials with iPSC’s off the ground (again, this actually did happen in September 2014.) Here’s what he had to say then, only a little over a year before that happened:

In her ISSCR seminar given 10 months ago, Takahashi presented some safety data from mice on the RPEs, but not from larger animals such as monkeys. To be clear, larger animal studies are not also not required, but this is an important distinction since larger animals are sometimes better models for humans and also because there were some anecdotal reports that said she had in fact presented larger animal pre-clinical safety data at the ISSCR meeting.

My understanding from Geron’s and ACT’s experience at the FDA here in the US is that the short-term nature of this iPS cell safety data along with very low animal numbers and lack of a clinically-relevant transplantation paradigm would be far from satisfying regulators here in the US that human studies should begin.

Unless there are a lot more, longer-term studies (e.g. 1 year or even longer) done on many more animals (e.g. 100s) yielding equally encouraging safety results specifically on transplants in the retina (not just sub-Q teratoma assays), I am deeply concerned as to whether the field is really ready to make the jump to transplanting iPS cell-based therapies into people any time soon.

Those long-term studies simply did not happen. There was never another large animal used in a study besides that one monkey (I have a copy of the study; I might post it later.) No additional long-term studies, certainly no hundreds of animals. I’m not sure about the transplant safety results, but I don’t really see how those could have been done when the long-term, additional studies themselves weren’t done. One thing we do know is that preclinical research wasn’t published until after this article (I want to say July 2013, but I would have to look this up.) Dr. Takahashi was given the go-ahead to start recruiting for the clinical trials in August 2013.

So what happened to the concern? Well, we don’t really know. It hasn’t been brought up in relation to the incredible rush to the clinic that the Takahashi study has turned out to be.

Here’s what I posted on Paul Knoepfler’s blog on November 18:

Paul, do you really, SERIOUSLY feel that only a year and a half later, anyone is really ready to transplant iPS cells into human beings? Isn’t a year and a half later “anytime soon?” Between your articles in 2012/2013 and today, we saw the STAP disaster take place at Riken, the SAME place that is responsible for the Takahashi trials. Some of the people involved are the same (such as Wakayama) Do you feel comfortable with the kind of self-policing that Riken has done since then? Do you think that all of the questions and concerns you had only a year and a half ago have been well addressed? Don’t you think there’s at least a real chance that these scientists are rushing terrifyingly and dangerously fast into human trials?

I just feel like the problem with the situation surrounding these human trials in Japan isn’t exactly rocket science. When pared down to its essentials, it’s pretty simple.

Ultimately, it comes down to this:
1.) Paul K. criticized the imminent rush to the clinic of iPSC’s in 2012 and 2013 in no uncertain terms
2.) He specifically said exactly two years ago that he didn’t think these cells would be ready for that IN TWO YEARS, which would be, well, today
3.) He listed some steps that he thought needed to be taken in order to be even a bit more confident that iPSC’s were ready for clinical human trials, and those steps weren’t taken,
4.) He brought up a ton of serious concerns, and now… can he SERIOUSLY be jumping on the rah-rah train? I don’t know if it’s exactly that bad, but he suddenly seems to have dropped all genuine criticism.

I really, really love Paul K’s blog, I think he’s an amazing scientist, he’s done so much good work, and I have so much respect for him… but when it comes to this issue, I think that he should return to his earlier and much more critical stance. Stem cell research is literally a matter of life and death. It’s worth being critical about.

Link to the Amazing msemporda’s Blog

There are a lot of stem cell blogs out there, some of them better than others… a LOT better. and some a lot worse. 😛 Paul Knoepfler’s blog is one of those at the head of the pack for sure, although I don’t always agree with everything he’s been publishing lately, especially the glowing, overly optimistic, heading-for-a-fall-IMHO coverage of Takahashi and her iPSC cell based RPE work in Japan. (You know, the one where they’re moving terrifyingly fast and using humans as guinea pigs about a zillion times faster than they should have…) But anyway. We all have our own opinions. 🙂

It’s also good to branch out. And that’s why I’m recommending this link to msemporda’s blog!

The Amazing Stem Cell Science Blog. THIS, I tell you, is an expert. Stem cell science, sector analysis, biotech company analysis, news… he has it all. And he’s somehow able to keep from rants…. I can’t do that, and I admit it… So check it out. 🙂