Dr Ed Wirth: Early phase clinical trials of human embryonic stem cell-derived oligodendrocyte progenitor cells in patients with subacute SCI

Puts in a plug for an org called scope. Among other things, there’s a comprehensive list there of current clinical trials.

Start with early fetal tissue work overview. Dr Wirth works for Asterias, and IS biased, which he cheerfully admits up front.

Shows an image of a cross section of a damaged cord. There’s a massive hole. Short of brain injury, sci is the toughest problem in science. During the 80s and 90s there were many studies that involved fetal tissue . . . these were about transplants that happened in the subacute phase, between 2 and 10 weeks post. You can fill cavities with these cells, and you can do it safely, at least in rats. If you put the cells in too early, they all turn into astrocytes and you get not only no function but more pain.

We’ve made mistakes. We’ve put olfactory cells into the cord and grown nose tissue there instead of neurons . . .

Showing a video from 1992 that shows a cat with a compression injury — a couple of months post the cat has some recovery. They gave her some fetal tissue and she recovered a lot of weight bearing and coordination. (I can’t really stand to look at this cat, who was injured deliberately, unlike the dogs we saw earlier. I know that’s not how all of you will feel.)

So what else? They did a little study of 8 patients back in the 90s — gave them fetal cells along with immunosuppression. All of them had been injured for many years and had syrinxes developing. Their condition was getting worse, which is probably why they volunteered for fetal cell transplants. Ed’s talking about a guy who had been injured for 25 years when he started losing sensation in his arms.

So Ed’s team got rid of the syrinx that was causing the problem and while they were there, they added a whole bunch of fetal cells — using what they’d done with rats for the previous 15 years as a guide.

Another case was a woman who was 30 years post, but had begun to lose proprioception and feeling in her legs and feet. Again, it was a syrinx causing the problem. She got the cells, but they didn’t survive once the immunosuppression drugs stopped. She could walk almost 4 times as fast. He’s showing video taken in Andrea Behrman’s lab of this woman moving along pretty well.

So.

Fetal tissue comes from elective abortions and there are ethical issues that will never go away. That — plus the need to have multiple shots on goal — drove the development of oligodendrocyte precursor cells out of embryonic stem cells. That work was done by Hans Keirstead in the early 2000s.  In 2008 Geron (the company that had funded the research) filed a 21,000 page request for permission to test the cells. In 2010 permission was granted, and a few patients were enrolled . . . but then Geron ran out of heart and money for the project, and it folded.

In 2013 a new group started over. The FDA didn’t like the way the trial was designed . . . they weren’t convinced that the doses were safe as planned, and they made the scientists go back. These cells, by the way, are derived from a single donated blastocyst from a couple that had all the children they wanted after an IVF procedure.

And they could make all the cells they would ever need for the next 100 years from the the cells they have right now. That means once the cells are perfected, they’ll be not just plentiful but CHEAP to make. It’s hard, though, to make them 100% pure. What can OPCs do?

So glad you asked. They can make myelin sheaths, they can produce neurotrophic factors and stimulate axon growth, and they can stimulate growth of a new tissue matrix. By now they’ve evaluated these cells in a whole slew of animal models. Mice, shiverer mice, rats, African Green Monkeys, Gottingen minipigs — thousands of animals. . . the animals were shown to get all kinds of improvement — unfortunately NOT in chronic phases.

Meaning, these cells didn’t work unless they were delivered during the subacute window — and that means if humans work the same as all the animal models, human patients would need to get the cells sometime between 2 and 4 weeks post-injury.

Now he’s talking about the first 5 patients who got those cells back in 2012. None of them got infections related to the cells, none of them had more pain. In 4 of the 5 subjects, there’s evidence that tissue matrices formed to fill the cavities.

In August 2015, the company that took over from Geron got permission to test more patients, and were careful to name the outcome measures using the SCOPE standards. The plan is to inject 2 million, 10 million, then 20 million cells.  The first cohort (the 2 million cell people) have been done & we’re waiting for the FDA to evaluate safety before cohort 2 gets the 10 million.

Boom, the end. That, my friends, was a ton of words all in a row. I maybe captured the gist. Go to the video.

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