“I want to help people breathe”
“I want to help people breathe“, he said and this is prominent in Dr. Silver’s mind. He is determined to make it happen. There is light at the end of the tunnel and momentum is building.
Dr. Silver’s research doesn’t require stem cell research. And it doesn’t require cyclosporine since he utilizes the patients own internal parts. Cyclosporine is used to reduce organ transplant rejection. He utilizes an autograft which uses one part of the patient’s body in a different location; therefore their immune system doesn’t reject the graft.
In short, he builds a bridge to connect part of the spinal cord above the injury to the corresponding part of the spinal cord below the injury. I created the visual aides below after watching Dr. Silver’s presentation. Their tests have been conducted on the front paw of rats and moved to testing respiratory improvements.
They call it a bridge because it simply bridges the gap. Like a bridge over water or you can think of it like a bypass on a highway when they do construction on the main road. Dr. Silver explained that the bridge is made by using a segment of the patient’s own peripheral nerve (there are thousands of these in the body). They choose one where the loss of a small segment of a nerve it not too detrimental. Typically they use a piece of the sural nerve or intercostal nerve where the resulting loss of function (mostly sensation) is not critical. An autograft is the term used to describe the action of moving this segment of the peripheral nerve to where it will be utilized.
To restore foot function in hemisected rats (only half the spinal cord affected) they use a nerve autograft plus an enzyme. An injured rat breathes shallower and faster, like a panting dog. Thus far for breathing they have only used the enzyme to stimulate nerve sprouting from the remaining side of the spinal cord to restore breathing capacity to 90% within 8 weeks of injury. The volume per breath increased and the frequency slowed down.
Dr. Silver would like to use the full treatment (autograft & enzyme) for breathing in the future so they can get closer to 100% return of function. His associate, Warren Alilain has written and submitted an abstract for the Society for Neuroscience and they will be attending the annual meeting in November. An abstract, in the science world, is a very brief summary or excerpt to a longer publication. And the scientists can read the abstracts and decide which meetings and topics to attend at the event.
My hope is that orthopedic surgeons, neurosurgeons, and urologists can apply Dr. Silver’s findings to assist in re-acclimating partial if not full function to hands, bladders, bowels, and legs to those in need.
At the end of his presentation I had a few questions for Dr. Silver.
Q: You know which nerves you are directing into the bridge, but does the body know what to hook them up to when you stick the other end of the bridge into the spinal cord below the injury?
A: That’s a good question. They go to where they’re needed. They don’t go very far. They don’t go up and down. And we’re targeting the end of the bridge to the place in the spinal cord we know is controlling breathing. If you get fibers to grow without a bridge you don’t know where they’re going to go. Our bridge lets us target the nerve fibers for a specific place.
Q: Since you’re ready to move onto primates, do you have an idea how long? Could it be another 10 years on primates?
A: No, if we could show we can bring back hand function, that’s the model in California, a C-5 lesion with just the enzyme trying to get fibers on the other side of the spinal cord to help move the hand. Right now it’s very slow it doesn’t work and we’re going to add the enzyme and we have a few other tricks to do. If a primate that uses his hand like we do can improve markedly, I see no reason why we couldn’t jump to human almost instantly.
Q: Okay so it could be 3-4 years away.
A: Maybe even sooner. The primate trials begin this year or next year and it could take just a year or two. As soon as we can show that the hand function in a primate is remarkably improved by simply injecting a tiny little needle, I don’t see why some neurosurgeon might write a IRB and find a couple of patients that are willing to do this since we do no harm by a simple injection. Now building a bridge is another issue because – that – you have to have a surgery.
So yeah, we would move to primates and go to human. We’re as close to going to human as we’ve ever been with this kind of success and no one else is getting it around the world – we’re doing pretty good. Nothing fancy, just an enzyme and a bridge and it’s taken over 20 years to get this far.
A little bit of background: When a doctor writes an IRB he is actually writing a proposal to his hospital requesting permission to do something specific such as using Dr. Silver’s technique on his human patients. This proposal is reviewed by the hospital’s Internal Review Board that the doctor works for (thus the name, IRB). Depending on the protocols it may require FDA approval but the details of that are beyond the purpose of this posting at this time.
Q: How can the regular person help you?
A: Like you? (yeah, like me – what can I do). It depends on how aggressive and proactive you are and who you want to talk to. We’re presenting this data; it’s now on-line in an abstract at the Society for Neuroscience meeting. http://www.sfn.org It may garnish some attention when presented at the meeting.
Q: How does this relate to chronic situations?
A: All of our work is in acute animals. Dr. John Houle, my partner, (Drexel University) and former student Dr. Veronica Tom are working on chronic. There is no obvious reason why it wouldn’t work. For them, they make lesion and wait six months and then put in a bridge and they’re doing that now. There is hope for chronic.
This is not cure but incremental improvement.
It’s just a foot but that translates to use of a hand.
Not walking, you’re not gonna get up and run away or play piano.
As you saw in our presentation, the movements in the rat were kind of sluggish but enough to keep it up on a running wheel.
This is one small step for rat, one giant leap for mankind.
Q: Thank you Dr. Silver.
A: My pleasure
How this respiratory testing will relate to humans with spinal cord injuries that affect that area for them is as follows. With all spinal cord injuries it is a case by case situation with how severe and bi-lateral the effects are. Basically, an incomplete injury could benefit from just the enzyme treatment. In cases of complete injury (such as the case with Christopher Reeves) a bridge would be required. At this time bridges have not been used in respiratory subjects and that is the direction Dr. Silver’s work is headed.
Having spoken with Dr. Silver since our meeting, I’ve learned that one of his former students is working with Dr. John Kaas at Vanderbilt University in Tennessee. They have begun the hand model testing on monkeys using the same technique Dr. Silver has used on rats.
From that very short phone conversation, I got the sense that the debates and discussions Dr. Silver expects to have will be related to distance issues – the length of the bridges needed to cover the lesions going from C2 to C4 for things such as respiratory issues and going from C5 to C8 for hand functions. These distances are not so far and he is confident the length will not be a significant factor. It certainly is a variable to be weighed and overcome but it shouldn’t be a significant factor.
The other issue will be chronic situations. It is yet to be seen if there have been changes in how the nerve fibers communicate with each other below lesions as time has passed. And, if there are changes how that will effect introducing a bridge to the situation. We do know that dormant nerves are capable of being revived.
I’ve enjoyed talking with Dr. Silver immensely.
I’ve learned a lot from him and he is doing incredible things!
Video Presentation Link
I am so very grateful and humbled by your interest in our lab. I haven’t had much experience with donations but you could simply send a contribution to me at my address at Case Western and also make a note on the check that this goes for Dr. Silver’s research. My address is: Jerry Silver, Department of Neurosciences, School of Medicine , Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106. Thank you for your amazing support.