Jan-Eric Ahlfors: Part 2 (Human Studies)

NOTE: This talk was delivered earlier today, but every slide carried a bright yellow line at the bottom declaring that the information on it was confidential and not to be shared without written permission. So I made a live draft, thinking I could catch up with Dr Ahlfors later and see what would be okay to post. “Later” turned out to be right before dinnertime . . . plus I had to do some thinking about how to discuss this material — which is why I’m just now getting back to it now, close to midnight.

Before I go further, I need to make sure we all understand the situation here. As Dr. Ahlfors told us yesterday, his path with respect to working on SCI is pretty unusual. You can refresh yourself with what I wrote during the first half of his talk here.  The readers digest version of that (plus some more info I’ve been finding on the web) is that after interning at a hospital, he went to work as an undergraduate in a lab & was encouraged to get creative by the PhDs and post-docs there. The lab is called New World Laboratories. According to its website, New World Labs …

… has not only invented a series of revolutionary platform technologies, but has also “re-invented” the classical (and lately not that successful) Biotech model: Instead of developing product ideas based on existing academic results and building companies around them, new technologies are being designed from scratch …

Jan-Eric is also the CEO of a non-profit known as the Novagenesis Foundation, which describes itself this way:

We are an example of how you must put aside dogma and courageously walk a new way to achieve. Innovate, design and build to succeed. Apply new thinking to areas of medical research and development that have failed to progress for too many years.

I have to say, this language sounds so much like what we in the SCI community sometimes mutter amongst ourselves when we’re feeling frustrated that it kind of scares me.

What Jan-Eric described yesterday was pre-clinical (meaning dish and animal) work that relied on NWL’s trademarked and patented technologies, namely a Regeneration Matrix and some Directly Reprogrammed Neural Stem Cells. Direct reprogramming is a process by which one kind of cell is manipulated with molecules to straight up turn into a completely different kind of cell. Again, sounds like magic.

But he described some very promising animal model results yesterday, and promised to talk about work in humans today. So that’s what this post is about.

Jan-Eric: Yesterday I was telling you about our work in the lab. Our company is called Ophiuchus, named after a constellation where new stars are born; it’s also associated with an ancient pre-Egyptian god. (You can’t say the guy isn’t ambitious.)

He goes on: So, yesterday we talked about how direct reprogramming works in neural stem cells, and how they’re more effective than other cellular approaches.

We’ve already taken these reprogrammed cells into four human patients with sci. They were all men, and all of them had been living with motor/sensory complete injuries for some time. (9 months, 18 months, 18 months, 26 months) The treatments happened between October 2014 and February 2015 — which means within the last 8-12 months.

This is the process:

  • At the hospital, a doctor takes a bone marrow sample, and it gets shipped to the lab (60 hours at most)
  • Direct reprogramming takes place at the lab (10 weeks)
  • Sample is shipped back to the hospital (max 10 days)
  • Doctor does 1 to 10 injections of the reprogrammed cells
  • Patient does rehab for 6 months to 2.5 years

The sponsor for this work is the Federal Research Clinical Center of the Russian Federal Medical-Biological Agency, which is receiving no money for their participation. They’re paying, not being paid. And all four of the patients he’s about to discuss are Russian.

Next we see a series of videos with English subtitles … a couple of the men who got their cells extracted, reprogrammed and returned to their bodies demonstrate that they can move their legs and feet while sitting up and lying down. One of them pulls his blue-jeaned knee to his chest, lets it fall to one side and the other, bringing it back to center without using his hands. There’s no question that he has muscles firing.

Later he describes being able to feel when he needs to empty his bladder, and the old familiar relief of emptying his bowels, and the return of a spontaneous erection.

There are charts and graphs that capture the exact places on each of the four bodies where sensation and movement returned; the last patient, who began with the most function, also got the most return of function. There’s a moving measure of electrical activity in formerly lifeless legs.

But there’s no formal documentation publicly available to show what exactly was done, or how.

Q: Are clinical trials still open?

A: Since the gov’t of Russia is paying for this, it’s only open to Russian citizens.

Q: Have you considered doing this procedure on best case scenarios? (Asia C/D?)

A: It would be pretty strange if it only worked on the worst cases . . . obviously it would be heaven to work on the best-case patients . . . we expect that it would work even better. We need partners . . . it all costs money & requires people; there’s much to be done.

Q: How will this become available in the USA?

A: The FDA would certainly require trials here . . . the goal is to get their permission. We really weren’t prepared for any of this return of function, but these patients have changed the timeline on which we were operating. We thought we’d have time after some safety studies. These were supposed to be safety studies.

Q: (It’s Naomi Kleitman, formerly of the NIH and currently Senior VP for Grants and Research at the Neilsen Foundation). When we speak to an audience like this, we have to be so careful. Going back to your stuff yesterday, you implied that regeneration had happened and that you were making new connections . . . you have to be careful about that and you have to show data. You showed some interesting functional restoration in people today. But patients do get the kind of recovery you saw over time . . . though yes, the movement in the leg is very cool. I really hope that you put your conversation in front of an audience like this into a little bit better context. We welcome that discussion. But if you’re talking about going to the FDA, you’ll have to clearly define your cell product, your manufacturing process . . . I just want this audience to keep asking questions.

And before Jan-Eric can really engage with the issues she raises, Barry says the 2 of them should talk offline … meaning that he thinks the whole group may not benefit from this kind of conversation.

So, what to make of this, friends? Is what we heard a convincing sales pitch or a genuine outside-the-box moment? How could we possibly be sure? The standard we usually hold scientists to is peer review. When the paper that outlines methods, materials, results and data is out there for everyone to read and discuss, that creates a certain confidence: this was done in a way that makes sense and can be replicated by anyone who has the protocol. When there’s no data to examine, what prevents an enthusiastic & well-meaning scientist from reading too much into his or her own work?

My skeptical self rejects anecdotal evidence; it’s too much like hearing patients who’ve gone off to get some poorly understood “stem cells” in India or China or Lima, only to find out that the stories of recovery weren’t reliable and the doctors doing the treatments can’t (or won’t) explain what’s going on.

My impatient self knows, though, that there’s a lot of wasted time in the standard way of doing things. What if this is the one time when doing an end run around the process worked? That would be amazing.

I don’t know which it is, though, and that’s my problem. I don’t have a way to know one way or the other. All I can say at this point is that it was a very interesting experience to be in the room where this material was being shown. With me were lots and lots of people sitting in power chairs, along with many scientists who have been doing the peer-reviewed paper thing for years, along with dozens of physical therapists and people from the NIH and the FDA itself. I could have listened to a discussion of this presentation for the rest of the day in that setting. I hope we hear more, and soon.

By the way, here’s a link to an article from a few years ago about Direct Reprogramming, for those of you who want more. It’s a very new technology.

Also, for any Russian readers who might be interested, the trial will be ongoing for another couple of years. Information is here.

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