Dr. Jerry Silver: Trailblazing Spinal Cord Research

32:46And so the synapse, the kiss between two cells makes a connection between an axon, a nerve fiber, and a dendrite of another cell. And this receptor, sigma, is involved with normal synaptogenesis. It's a very sticky receptor. But this same sticky receptor is appearing in great abundance on the cut nerve fiber. When the nerve is cut in a spinal cord injury or a stroke or in a degenerative disease, it upregulates, it increases the amount of hooks. It changes the type and the amount of the hooks. They make way more. Now there are zillions of hooks around on the cut nerve fibers. And don't forget the proteoglycans are present in the scar.

33:36So they make lots more of the receptor. So how do we get rid of it? In my lab, we decided to block the receptor by using what's called a peptide. And that peptide would bind to the hook and it would block it. It would make it non-functional. It's like taking the part of Velcro that has the hooks and smearing it with molasses or glue. Just cover up all the hooks. right so now they can't even see the pro they can't hook on to the proteoglycans so that peptide we call intracellular sigma peptide or isp and in our nature paper in 2015 we described this peptide for the very first time the peptide has a shuttle attached to it It's called TAT, T-A-T.

34:27It's a sequence of amino acids that helps the peptide get across membranes. It's based on HIV infectability. HIV can get into your body easily, mostly through sexual contact. And that TAT part is a shuttle that allows that virus to go through your tissues. So we used TAT, T-A-T, and attached it to our peptide, which blocks the receptor. It's called a wedge domain. So the part of the receptor that causes its activity is called a wedge. That's not so critical. So our peptide blocks the receptor and gets through the tissue, even if you just inject it just subcutaneously under the skin of the stomach.

35:23So it's a TAT peptide, T-A-T slash peptide. And that you can put anywhere because TAT, like HIV, takes that peptide all the way into the brain and it takes it all over your body. So you don't have to touch the spinal cord. You just inject it subcutaneously under the skin of your stomach or your back skin. So then it gets into the brain and spinal cord and it blocks the hook. Now the receptor is blind. It can't see the proteoglycans and the nerves regenerate. And they sprout like crazy. They no longer see the loops. They just grow right past them. I have some dumb questions. Please. The dumber the better.

36:04Okay. Dumb question number one is, if you're blocking this process, how come now all of a sudden you give this to patients and things aren't growing into their pupil? Have you stopped that process? Very good question. So remember what I said just a few minutes ago. Let's stress it. When the nerve fibers are damaged by a spinal cord injury or a stroke or by a neurodegenerative process, those nerve fibers upregulate, increase dramatically the number of those hooks. They increase dramatically the number and packing density of that receptor. So they make lots more. for some unknown reason. So now, if you give the peptide, those are the first cell types that are affected because they have so much receptor.

37:03So you can play around with the concentration, how long you give it, and those are the first ones that are targeted because they make so much. Now, that's not to say that your question is dumb at all. Your question was actually brilliant because one wonders if you give this peptide for such a long period of time that it changes the way the connections in the brain are hooked up or when the nerves regenerate when you give the peptide are they going to be able to make connections or are they going to just keep growing wildly and the answer to that question is in the animals we give the peptide for seven weeks not forever and then we stop and then the animals continue to get better after we stop giving the treatment it's conceivable that in the presence of the peptide for very long periods of time those regenerating nerve fibers don't make very good connections because we need the receptor to make the kiss the synapse so now you stop giving the peptide and you ask me how long do you give it.

38:14That was one of the first questions you asked me. How long? And we really don't know what's the optimal time. Should you give it every other day? Then the nerves that grow can make a connection. Or do you stop after two months and the nerves that have regenerated, they can make connections. Or do you give it for a year and then stop? See, we really just don't know the optimal timing and position for the best route of administration yet. That's something the company has to work out. And the best way to work it out for people is going to be in patients. So the very first patients, if they report that they are still improving when NerveGen wishes to stop, in that trial, they'll have to stop when they said they would.

39:01But they can do another trial where they give the peptide for much longer or in much higher concentrations or deliver the peptide in a different place. That could be better. Okay. Dumb question number two. Please. Are you essentially saying that this treatment doesn't fix the problem? It enables the human body to fix the problem because the process was being blocked. That's right. Very good. Again, a brilliant hypothesis. this. Basically what we're doing is helping the body, and in this instance the spinal cord, fix itself. The nerves have the capacity to grow, not as fast as their embryonic counterparts, but they can grow.

39:49They can grow towards proper connections. We have seen that in our animals, the animals get better, not worse. So the nerves that are regenerating and sprouting seem to be able to find the proper partners to connect with. The animals don't throw themselves off the table. They don't do strange things. There's no unbelievable spasticity or weird dystonic type of postures. The animals get better. They can walk better. And we just had a paper accepted for publication. They can actually use their fingers better, depending on where you put the lesion. If you give the peptide then, they can use their hands better, their fingers better, and they can walk better.

40:36Not worse. So somehow Mother Nature is allowing the connections to be functional rather than non-functional. Now, I can say one thing. There's another paper that you might know about that has been published where we studied the use of chondroitinase, not the peptide, the chondroitinase enzyme in a breathing recovery model. And in that paper, we report two very important things. One, the longer you wait after the injury to give the enzyme or the peptide, the better the result. The longer you wait after injury, the more chronic the condition, the better the results are when we get rid of the hook and loop interaction.

41:23there's some kind of reconnections that are forming very slowly we think that are being smothered by the proteoglycans all right so that's very important so people who have very long chronic spinal cord injury should not be depressed as a matter of fact they should be quite happy. So there's no reason that 20 to 30 to 40 years after your accident that caused a paralysis, there's a lot of new connections that have been formed in the spinal cord, in the area of the lesion and elsewhere that are being smothered by the hook and loop interaction. Now, when we give the peptide or the enzyme, those connections that are smothered wake up very, very rapidly.

42:14Do you remember when you asked me how long it would take for people to get better? And I said it would happen very quickly within weeks. That's what we've seen. The longer we wait, actually using the peptide or the enzyme in acute injury was not nearly as good as chronic. Up next on Remarkable People. I wouldn't call myself a pioneer, but in the modern age of science that goes back to my earning my PhD most people in the neurosciences studied neurons and I guess it's just the way I am I just like to do stuff that other people don't do and I have a weird stubborn streak so if I see something that I'm sure is right because I see it in front of my own eyes I become very persistent.

43:05become a little more remarkable with each episode of remarkable people it's found on apple podcast or wherever you listen to your favorite shows welcome back to remarkable people with guy kawasaki i was gonna ask you for clarification on this and i think you just explained this this interview i listened to of you said that there was a very fortunate accident where your research assistants went down and looked at rats that were like 18 months ago. That's right. And lo and behold, the rats that had this for 18 months had great progress. Is this what you're alluding to? That's exactly right. Most people in our business, spinal cord injury business, the field, don't study chronic injury.

43:56They're very high risk, although high reward experiments. They're extremely expensive because you have to keep the animals around so long and animal care is expensive. But my student who was an expert in the area of breathing, spinal cord injury that affects breathing in the spinal cord. So this is a very high cervical injury, which by the way, most people get. Most people are injured in the spinal cord in the cervical area of the neck. because it's so flexible and tends to get hurt. He had made lesions in our rats at a high cervical level that paralyzed their diaphragm on one side. You can't make the lesion all the way because the animals can't breathe.

44:40So it's a partial lesion that paralyzes half the diaphragm. And we were injecting the chondroitinase enzyme and using our peptide acutely after that injury and seeing very poor recovery. Almost not. I was actually very depressed when my student, his name was Warren Allelane, first arrived in the lab. I said, well, Warren, let's do something else. And we did. But he had lesioned 12 animals, 12 rats, in the high cervical spinal cord. They were in the animal facility, and he'd forgotten about them, that they were even there. And he forgot about them for over a year. And he discovered them. one afternoon and came up to my lab.

45:28I will never forget the day he came into my office. He says, Jerry, guess what? I'm sorry, but I lesioned a dozen animals over a year ago and forgot about them. They're in the basement. What are we going to do with them? I said, well, I don't know. We can't throw them away. It cost me about$5 ,000 just to keep them down in the basement in the animal facility. So I said, let's inject condroitinase and see what happens. This is before the peptide. So he did. And he came running back in the next few days. He said, Jerry, the animals are breathing. It's incredible. So then we needed more help. So another six months passed, and we hired a postdoctoral student who's from England.

46:13Her name was Pippa Warren. So it was Warren Allelane and Pippa Warren. And when Pippa came, she did this study really well. and the recovery of the diaphragm on the side that had the lesion. So the animal had been paralyzed essentially all of its life. And within one week after injection of the chondroitinase enzyme into the spinal cord near where the motor nerve cells are that move the diaphragm, within one week they started to breathe. And within two weeks, after injecting the enzyme, the breathing, the amount and the depth, the quality of the breath was equal to that of the other side. It was completely normal.

47:04Completely normal. Complete recovery of diaphragm function. And we also saw improvements in the ability of the same animal to use the forepaw. which is also paralyzed from that lesion on the same side. Now here's the other part of the story I was going to tell you. So from those experiments we learned that longer is better. We found that an optimal time after the injury to get recovery is you have to wait at least three months. At least and almost nobody in my field waits three months. They wait one week or they wait one day and then they treat and then they report their results. Minimum of three months, but the longer you wait, the better.

47:51And the quality of the breath and the amount of unusual changes is very small. Now, let me add the second part. In some of the animals, if we gave the enzyme to the animals that were about three months after their injury, and we pushed the animals too hard with their respiratory therapy, and that therapy was called intermittent hypoxia. So we basically forced the animals to go to Denver for five minutes and then come back to Cleveland for five minutes. So they go up to Denver and breathe low oxygen air, then they come back to Cleveland for five minutes, they breathe normal oxygen air and back to Denver and then back to Cleveland and you alternate that.

48:38That's called intermittent hypoxia. That's respiratory rehab. When we did that in our animals, and these are mostly three months after injury, when we pushed too hard, when we gave the enzyme and lots of intermittent hypoxia, then we saw some problems in the diaphragm. It was too much of a good thing. It was bad. The side of the diaphragm that had recovered was now spazzing and not breathing properly. Now, that would go away. It would fix itself in about two weeks, but you don't want your patients to have a spastic diaphragm or a spastic arm for any time at all. So, we found that you can't push too hard.

49:24So, the amount of rehab you give has to be the right them out, not too much, at least for the diaphragm. And that's a warning. I can explain that. So what happens is when you give the enzyme and you give intermittent hypoxia, one of the nerve fiber tracts that regenerates and sprouts like crazy makes a nerve transmitter called serotonin. Some of you may have heard about serotonin. You may have, because serotonin is really critical for anxiety. And SSRIs like Prozac increase the amount of serotonin that's interacting with its receptor in the brain. So more serotonin is good if you're anxious. SSRIs.

50:10But too much serotonin, way too much is bad. That's the way mother nature is. It's got to be the right balance. Too little is bad. Too much is bad. And we found out that in the animals that had this bizarre spastic diaphragms, there was too much serotonin. We had to back down. Yeah. So people can overdose on SSRIs and they get horrible spasms and they get crazy hallucinations. So you can take too much. So that's one of the drawbacks. You can't push too hard. It seems to me the way you describe all these discoveries over the course of 30, 40 years, It's pretty exciting and has major ramifications.

50:56And yet I read that if it wasn't for some dentist whose daughter became a paraplegic, we might not be having this conversation. So I don't understand, like, why was it necessary for this dentist to rekindle this interest? That's a very important question. Let me tell you a little bit about the story that led to the licensing of our peptide and the establishment of NerveGen. We had published our nature paper on the discovery of our peptide in 2015. The receptor itself, Sigma, the hook, was discovered in 2009. So between 2009 and 2015, we were trying to figure out a way to smother or cut off the hook.

51:48And we had made some advancements that were unpublished before 2015. The work was being done, but it hadn't been published yet. Our story was pretty ripe already around 2012, 2013. and fortunately our university has some connections with big pharma and actually invited big pharma and this one happened to be GlaxoSmithKline to Case Western Reserve to hear the good stuff that was happening at the university. One of the tech transfer people at Case Western was from GSK and knew some of the big shots in that company and invited them to come. And they said, okay. And so we had a GSK day at Case Western and they marched a couple of dozen labs in front of these guys.

52:47I was the last roadshow of the day. It was around four o 'clock, 4.30 in the afternoon. Everyone was tired. And I presented our story about our peptide and our walking rats and the chondroitin sulfate receptor interaction. And they loved it. They absolutely loved it. And we talked more and we actually formed a partnership. And this was around 2010, 2011. And we were rolling along really well. Actually, GlaxoSmithKline gave us some money to do some very critical dosing experiments. They assigned a group of people at GSK to us. They had a program at GSK at that time to fund basic research in different universities for promising translational science.

53:40And we were rolling along. And now, finally, comes time to ratchet up the funding, to bring this in-house and do it right, and mass-produce the peptide, do all the important control experiments, and move to people. Unfortunately, I will never forget this day. I was sitting in the office with the person who is the friend of the person at GSK. We were sitting in the office waiting for the phone call. Is it a go or no go? And the answer was no go. Why? Oh, it was so depressing. And the reason was spinal cord injury is a small market, and GlaxoSmithKline likes to make a lot of money. And we were studying mostly acute injury at that time.

54:30We hadn't made our animals in the basement mistake yet. So the number of people who are paralyzed in the United States each year is around 16 ,000. And that's an orphan market. It's very small compared to Alzheimer's disease or multiple sclerosis, where the numbers of patients are in the millions. And the amount of money to be made, obviously, in Alzheimer's disease or MS is huge compared to spinal cord injury. And so the upper level management made a decision to abandon the program. They then suggested the possibility, I think at that time, the company called AbbVie, who makes Humira, makes a fortune from Humira, AbbVie.

55:14And they have a lot of new drugs on the market these days. So AbbVie, I think it's A-B-B-V-I-E. They suggested we talk to AbbVie. And so they loved us too. And AbbVie got very interested in the possibility of licensing our peptide and doing a clinical trial. And we spent another year doing experiments. And then they had a special team appointed to us and upper level management again. No go. Too small a market. They wanted us to study multiple sclerosis. We hadn't done our research using an MS model until later. Actually, the peptide NVG291 and our peptide that we use in rats called ISP has beautiful effects in MS models.

56:05So spinal cord injury is not the only target of NVG291. The cells that make new myelin also have the same receptor. And in the MS plaque, you see the same proteoglycans all over again. It's repeated. AbbVie wanted us to already have data on multiple sclerosis, which we did not, so the project got killed. And now we have nothing. Nobody. And time is passing, and the clock is ticking, and I'm getting older, and nothing is happening. Because Case Western does not have unlimited contacts with big pharma. We were dormant until Harold Punnett. I can't remember exactly what year. It's been seven years.

56:53So is this around 2016? Yeah. Around 2016, I started talking to Harold Punnett. Harold is a dentist. He's in Canada. He is a wonderful guy. And unfortunately, his daughter-in-law was paralyzed in an accident. She fell and broke her back and became paraplegic. And Harold, the dentist, who has some knowledge about biology and science, was searching the world for something that could help. It's his daughter-in-law. And he couldn't find anything until he happened upon our paper, which was published in 2015. And he got really excited about it. He's also an angel investor. He's done this before. It's one of his, I guess, hobbies to invest in startup biotech companies.

57:47And he knew some investors in Canada who might come along with him. And Harold and I talked and talked. And we got along beautifully. He's a wonderful guy. He's just a nice guy, brilliant. And he wanted to start a company. And so he brought in a few other people. And NerveGen was born. Wow. It took a while for Case Western to negotiate the deal. It took years, actually. Wow. That's just kind of the way Case Western works. But there were several points during the negotiations that were very tense. The university wanted more. The company wanted more. You know how it is. So the negotiations took a while, but they were successful.

58:32I am told by the people at NerveGen they would have never walked out, ever. They were prepared to negotiate for as long as it took. It took a while, but eventually, thank God, NerveGen was born. And in a few weeks, the culmination of 40 years of my work is going to happen. And the first patients with spinal cord injury are going to be injected with a peptide. So fingers crossed. Actually, thank you. It's not a slam dunk. You never know. Rats are small. People are big. Rats are all the same size, same weight, same genetic background. Everything about white rats is pretty much shared from one animal to another.

59:20Humans are all different. We don't look alike. Our genetics are different. We're different sizes, shapes. Okay. Just the way it works.

59:39so i hope this story is true but you know what wd-40 is sure it's one of my favorite i spray it on everything so the story goes that wd-40 it represents the 40th attempt at the formula really so is nvg 291 basically the 291st attempt at creating this peptide no i don't even like that name i wanted to name it something sexy like regenovid or something like that and nvg is nerve gen i don't know why it's the first iteration it's a humanized version of the rat peptide it's designed to work the best in people i have no idea you'll have to ask somebody at why do they pick 291 i have no idea it's actually nvg1 hopefully there'll be a 2 3 and 4 but i don't know okay and this is my last question so okay first pardon my scientific ignorance but i think that what the glia does is it makes these physical barriers and inhibitors that protect neurons right correct okay so now i read or heard someplace that you have license plates that say glia man oh no now it would seem to me that by making license plates that say glia man you are in fact highlighting something you're trying to undo because you're trying to end the protection of neurons and stimulate regeneration right so why clear man in the first place i wouldn't call myself a pioneer but in the modern age of science that goes back to my earning my phd most people in the neurosciences studied neurons.

1:01:46And I guess it's just the way I am. I just like to do stuff that other people don't do. And I have a weird stubborn streak. So if I see something that I'm sure is right, because I see it in front of my own eyes, I become very persistent. I'm unflappable. And so I believe that the glia were important. They must be doing something other than being nurses to the neurons. That's what people thought. Glia just support the neurons. But I believed that the glia impart important information to the nerve cells. They help them work better, we now know, but also they get in the way sometimes. And one of their jobs of a glial cell called the astrocyte, which means star-shaped astro, sight means cell, which are the most abundant glial cell types in the brain.

1:02:38It's not a nerve cell. It doesn't fire an accident potential. It's a glial cell. It looks like a star. They're everywhere. The astrocytes have another job, and one of their jobs is to make a scar. Just like fibroblasts in your skin make a scar, you want to stop the bleeding, and you don't want the infection that could occur in that site to spread all over your body, you make a scar. But we don't have fibroblasts normally in the brain, so the astrocyte plays a role in building so-called glial scar, which surrounds the area of inflammation that you might get after a small hemorrhage or a bump on the head.

1:03:25And that scar that the glia makes serves an important purpose. It walls off the area of injury so it doesn't spread all over your brain. Sometimes the scar actually responds to tumor cells that have invaded your brain. And if they trigger the scar, the tumor in your brain will be round like a golf ball. Unfortunately, glioblastoma, which is a tumor cell that's very clever and have fooled the astrocyte into not knowing it's even there does not create scar. And unfortunately, glioblastoma migrates all over the brain. So the glial scar plays an important role. Unfortunately, it also blocks nerve regeneration.

1:04:13Now, can you get rid of the proteoglycans or get rid of the receptor on the nerve cells and not do damage to the scar so much that it allows the inflammation to spread all over your brain. And apparently, you can get rid of the proteoglycans with chondroitinase, but the wall-building ability of the scar still remains. Because Mother Nature has not built a scar just using proteoglycans. she also makes the cells the astrocytes very interconnected what are called adhesion junctions so the astrocytes that make a scar are all welded to each other with are called adherence junctions see mother nature's smart she doesn't use just one mechanism to build a wall she also takes the astrocytes and makes them really big and she makes them really convoluted shapes no longer are they parallel or nicely shaped they are bizarre like spaghetti bigger shaped like spaghetti all welded together in a wall and they make proteoglycans one two three four different so you can get rid of of proteoglycans and still have a wall and so you don't have this okay expanding lesion so so that's what mother nature does thank god we can get rid of the proteoglycans but the wall building function is still partly there but the nerve cells can now get through or across the wall okay this is truly my last question you've been at this for 40 years that's right luckily a student left some rats in the basement and luckily a dentist made contact with you.

1:06:05So as you look back on these 40 years, what's the lesson here? What's the lesson of Jerry Silver? That's a good question. I don't know why I am the way I am. It probably has something to do with the way I was raised by my parents. I don't know. Maybe it's having a Jewish mother who used to tell me crazy things that I thought were wrong. And I had to base the way I am on my own beliefs. Because my mother was telling me crazy things. You know how Jewish mothers are. If you don't eat enough, or you can go blind if you do the wrong thing. And all kinds of crazy things about who you can date, who you can't date.

1:06:45And so I had to make up my own mind about what I see. And I've always believed if I see something in front of me with my own eyes, it's true. So that's how I started. If I would see something that everyone said was wrong, even my mother, I said, I'm sorry, it's wrong. I'm right. And I have carried that with me all my career. and if there's anything to say about who jerry silver is it's that i'm stubborn uh i i believe in myself and if i see something that i think is true even if the rest of the world says i'm wrong i stick with it and i've been doing that for for 40 years and the proteoglycan story don't forget people in my own department said i was studying artifact i can't tell you a very interesting phase of my life where my story came to fruition in another company, which is a rags to riches to rags against story that you might be interested in.

1:07:53I was studying proteoglycans for a long time, right? Since the mid-1980s and late 1980s, and we published the first paper, 1990. So right about the end of the 1990s, another company came to Cleveland that I founded, And the company's name was Gliatek because I'm Glia man. Gliatek was the very first biotech company in northeastern Ohio. And there was a fellow at Case Western who was just looking around for technology that could be promising and translational. And I told him the proteoglycan story. I said, they make barriers. But back then, Gliotec had a different story that actually went all the way to an FDA-approved product and was used in hundreds of thousands of patients.

1:08:45My idea back then was to build a barrier where you would actually want one and use proteoglycans to do this. Where do you want a normal barrier? If you know about nerve entrapments, for instance, you know about carpal tunnel syndrome. You've seen people with carpal tunnel. The median nerve and tendon get entrapped and scar. So scarring in the body is very bad. So you can get scarring in the uterus or around the uterus. It causes infertility. You can get scarring in your abdomen that binds to your GI system, and that's bad. Scarring after burns of the face or an operation that's gone wrong, like a tracheotomy, a big scar.

1:09:28So scarring is bad. I thought, wouldn't it be interesting if we could get rid of scars inside the body? And Gliatek was born on a completely different patent that I had generated. It's not important. But I told him about my idea. And what Gliatek did was to say, let's put a barrier where we want one. So if you damage a peripheral nerve, say in your elbow, say you damage your ulnar nerve, and that nerve gets entrapped in scar tissue, or if it gets entrapped in your wrist in scar tissue, that's extremely painful. So nerve entrapments in the body are very common. If you cut your wrist with glass and you get scar tissue around the nerve, the median nerve, Oh, it's terribly painful.

1:10:24It's called nerve entrapment. That scarring that tethers the nerve causes unbelievable pain. It turns out that proteoglycans inhibit not just nerve cells. They inhibit all kinds of cell types, even fibroblasts. So my idea was to make a barrier out of proteoglycans and make it into a gel. so it could be squirted into the area where the nerve damage and cover up everything. And Gliatek invented a product called ADCON, A-D-C-O-N. They were going to use it in surgery on the back after you get a discectomy and people have ruptured discs. One of the horrible things that can happen after a discectomy is nerve entrapment of the dorsal roots, which is unbelievably painful.

1:11:15It's called failed back syndrome. So that's what they were going to target first and other nerve entrapments. So they called this product Adcon-L. You can Google it and find out. Basically, Adcon-L was gel foam powder, which is a collagenase powder, a glycosaminoglycan that was synthetic called dextran sulfate, not chondroitin sulfate, and water, buffer. That was it. it made this beautiful anti-fibrotic gel and if you have a nerve entrapment you could go in as a surgeon cut away the nerve the adhesions but unfortunately the patient would get better because you cut away the scar loosen up the nerve but many people develop scar again and if you go back and cut away the scar around the nerve they get relief pain goes away and in six months or a scar comes back, always worse than the time before.

1:12:17And after four or five surgeries to, it's called neurolysis, to free up the nerve from the scar, you can't operate anymore. And AdCon L was invented for those patients. Amazingly, one of the first patients in the United States was named Mr. Smith. Right around 1998, with FDA compassionate approval, Mr. Smith had five surgeries on his wrist because he had cut his median nerve. Not completely, but he had a terrible scar in his wrist. He had so much pain he couldn't sleep, he wanted to have his arm amputated. And he was the first American patient to receive Adcon-L. After his fifth neurolysis surgery, he was cured.

1:13:04And Adcon L was used in all kinds of interesting other types of areas where there was scarring. Tracheotomies gone bad with scarring around the trachea and the larynx, scarring in the face because of dog bites. Adcon L was fantastic. Gliatek was rolling along. They were on the NASDAQ exchange. The stock price was soaring. And then that's my riches part. Rags first, riches, and then the company screwed up. The company had very greedy, selfish people. You hear about these kinds of people from time to time in the United States and elsewhere where they take a perfectly good product and ruin it because of greed.

1:13:50And unfortunately, that happened. It's a longer story and you can read about it. The FDA blackballed. But that was my first successful biotech company. AdCon had been used in over a half of a million operations around the world. So lots of people got better. So that was my first experience. AdCon, L, Gliatek, and an FDA-approved product within just a few years. And the company went bad and fell apart. So after Gliatek fell apart, I was very down on forming yet another company because of the bad experience that I had with Gliatek who killed my baby. So now my attitude, I was very scared, fearful of forming another company where the same thing could happen to me all over again.

1:14:44That is greed at the level of the company management. Now, I am convinced and extremely happy with the upper level management at NerveGen. I'm not afraid anymore. I believe that now, instead of putting a barrier where we want one, we're going to get rid of a barrier where we don't want one. It's very similar, in a sense, to Gliatek, which was quite a remarkable success. They were predicting billion-dollar market until they screwed it all up and the company went broke. You can read all about it. There are lots of essays about it and the history of Gliatek. And when NerveGen came along, I had to convince myself that everybody was honest.

1:15:27They're not in it just for the money. They're in it because they want to really help people. Of course, helping people can be profitable. I don't have any problems with the company making a great profit. That means they're successful and people will be getting better. But I believe that NerveGen is really meaningful and they are going to target spinal cord injury first. So I'm so happy. until finally, after all these years, they're going to target. And with the failure of GSK, the failure of AbbVie, finally, with a startup biotech company in Vancouver, I have hope. They're not going to screw it up.

1:16:05Now your mother will be proud. Yeah, right. May she rest in peace. Yeah. I hope you enjoyed learning about the advanced work of Jerry Silver, truly a pioneer in the field of spinal cord injuries. His discoveries and explorations have shed new light on possible treatments for conditions that are life-changing. This makes him truly a remarkable person. I'm Guy Kawasaki. This is Remarkable People. My thanks to Merge 4, the coolest sock company, for sponsoring this episode. Remember, use the promo code FRIENDOFGUY to get 30 % off. My thanks to the incredible, remarkable people team. Jeff C., Shannon Hernandez, Tessa Nismer, her sister, Madison Nismer, the drop-in queen of Santa Cruz, Fallon Yates, Louise Magana, and Alexis Nishimura.

1:17:10Until next week, mahalo and aloha. This is Remarkable People.