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Bringing the dead back to life is a plot often heralded by science-fiction enthusiasts, but advancing medical technology is moving it closer and closer to becoming reality. BTRtoday spoke with Ira Pastor, CEO of Bioquark, about ReAnima–a groundbreaking trial that aims to reanimate the brains of the dead through comprehensive neuro-regeneration.
BTRtoday (BTR): Tell us a little bit about how you became involved and interested in this project.
Ira Pastor (IP): Bioquark has spent the last several years studying a unique form of regeneration called epimorphic regeneration, which occurs in nature, primarily in lower organisms. You’re probably familiar with the ability of salamanders to lose substantial parts of their spinal cords or limbs and have them grow back in perfect form and function in just a matter of weeks. What is lesser well-known is these same species are exceptionally good at regenerating all of their crucial organs, including their central feverous system and their brain.
And so this initial research led to our program, trying to figure out how we could translate these capability to humans, because humans are really devoid of them. We’re very good at putting down scar tissue, but aside from that we have very minimal regenerative ability in any of the critical organs or tissues that keep us alive. Hence, the interest to explore this space—the general central nervous system space of course, but the wider ranging disorders of consciousness, and brain death.
BTR: In these trials, what are some of the therapies scientists will be using?
IP: We have the biologic tools and the medical devices that are typically used in the ICU to stimulate coma patients to try to wake up. The core of what we do is less about the cells, but how you basically teach that part of the body to realize what is missing, and what to reform. And this capability is what the salamanders and the worms and the starfish of the world are so good at. So we’ll be using a combination of biologics, peptides, and other bio-products to stimulate that capability in the nervous system that says we’re going to start over.
From this point, we know that a brain stem and the higher brain and so forth should go in this spot, and not a heart or a brain or an eyeball. This is extremely important, and it’s why lower organism regeneration is so effective.
BTR: And you use stem cells to achieve this?
IP: The stem cell-centric approach, if we were just applying stem cells, you’re not going to get anywhere because if you go inside the brain of somebody in this condition you have an environment that knows nothing about regeneration; it’s full of inflammation and dead tissue. There’s really no direction as where to go to next. So that’s why we’re combining the biologic approaches with stem cells, and things like median nerve stimulation–like transcranial lasers–that are typically used as ways to stimulate the system to try to wake up.
BTR: These protocols have been heavily standardized and approved by the Institutional Review Board (IRB). Was the approval of the project difficult to achieve?
IP: This type of research falls into an area not as well-known as living cadaver research. Basically we’re dealing with individuals that have been pronounced braindead who are still on cardiopulmonary support, so they’re still breathing, their heart’s beating, they’re being supported by nutrition and other atrophic factors to support the rest of the body. It’s not the sexiest area of biomedical research, but it has gone on for decades, in the United States and elsewhere.
It was difficult to achieve in the context that it’s the first time something like this has been attempted. From that context, we were on fairly sound footing with the ethical committee and the IRB approval. The context that we were doing this for a slightly different purpose in terms of neural regeneration took a bit of convincing to actually approach a family with this option versus donating your body for some of the strange testing that goes on with cadavers nowadays. That took a little time, but in general our point was understood, and we succeeded in getting the approval–not just from the committee, but also the extremely comprehensive family-informed consent.
BTR: In phase one, you’ll be choosing 20 trial participants. What is the process like for choosing the participants?
IP: It’s really a matter of the family choosing at this point, when they get to stage in the ICU where there’s nothing that can be done in this particular case. Your options are organ donation, or this experimental option that we now have available. That’s when the family makes the decision, but needless to say, recruitment for this is not on the patient per say, but on the family and their particular interests.
BTR: You talked about how salamanders can regenerate entire limbs and organs, and how this is similar to the idea that brain stem cells could be used to erase and start over in surrounding tissue. Could you explain that a little bit more and break it down?
IP: There are five types of regeneration in nature, and humans have three of them. We have physiological regeneration of the cells that actually turn over, so our blood, outer layer of skin, hair nails, and what have you. We have a hypertrophic regenerative response, primarily in our liver, where if we lose part of our liver in some event, the liver will not regenerate in form, but it will grow in size in the amount of cells to replace function.
Then we have probably the most important thing, and it’s one of our Achilles’ heels in terms of complete regeneration, and that is our wound healing response. We are a species that bleeds very rapidly and we die of loss of blood very rapidly. Evolution has sort of biased things toward a very comprehensive thrombotic and fibrotic wound healing response. These are all, in essence, forms of top-down regeneration: where cells are recruited, a la stem cells, the progenitors, and they quickly seal upon a wound, but they don’t care too much about restoring the function or complete form.
In lower organisms it’s a little different, because some of these don’t bleed a lot, and as a result from an evolutionary standpoint, they’re less concerned biologically with the loss of blood. The biologic process is more focused on recapitulating development. Basically, signals are sent out that say something is missing, and then the development process resets from that particular point and moves forward until completion of the development process again. Amphibians can do it throughout their lifetime too; it doesn’t matter the age of the organism. They can very effectively recapitulate both forma and function.
BTR: These lower organisms seem far more capable of withstanding death.
IP: Interestingly, these same species that are so good at regeneration are some of the most cancer-resistant on Earth. It has nothing to do with the fact that they don’t get cancer; everything on Earth gets cancer at some point. How they deal with it is much different than how we deal with it. They don’t try to kill anything. Similar to the reprogramming during regeneration, they focus on reprogramming the tumor tissue and just turning it into normal tissue.
There are some very interesting clues here on the regeneration side of things to affect other potential outcomes. Regeneration and cancer have always been part of this double-edged sword, but yet you have these wonderful regenerators that really have this cancer situation taken care of, unlike us.
BTR: There’s been comparisons to your trials to resuscitating people from heart attacks. What are your thoughts on that?
IP: The resuscitation technologies at that level and some of the things that are occurring now like therapeutic hypothermia or cooling the body, these are ways to prevent brain death and prevent the cascades that occur following a stroke or a heart attack or what have you. These are very useful in helping prevent clinical death. Clinical death is something that happens all the time—it’s the temporary stopping of your heart and lungs, which we’re pretty good at restarting nowadays.
The brain is a little more complex, but at the end of the day when you think back, we’ve been transplanting hearts and lungs for a pretty long time now, so we think in spite of the irreversible label that brain death has had attached to it since 1968, it’s 2016 now and we think this is a pretty viable point in time to explore this current definition.
BTR: What kind of future implications do you foresee these therapies having for severe disorders of consciousness like Alzheimer’s and Parkinson’s, for instance?
IP: We think substantial. All of these that you mentioned, be they chronic disorders or acute, ultimately are all situations of cellular damage and regeneration. And if we can learn from the most severe cast—brain death—the knowledge will be invaluable and trickle down to coma, persistent vegetative state, minimally conscious state, and then all sorts of central nervous system (CNS) disorders. We think this research has wide ranging possibilities on CNS and beyond.