Page 2 of 7 FirstFirst 1234567 LastLast
Results 11 to 20 of 62

Thread: Potassium Channel Blockers to Restore Impulse Conduction in SCI ? Dr. Riyi Shi

  1. #11
    Senior Member lynnifer's Avatar
    Join Date
    Aug 2002
    Location
    Windsor ON Canada
    Posts
    19,314
    I've not seen where a rapid heart-rate is a side effect of Fampyra? Side effects lasted for two weeks and then went away for me, except the insomnia .. but I've been taking melatonin for two weeks and things are much, much better!
    Roses are red. Tacos are enjoyable. Don't blame immigrants, because you're unemployable.

    T-11 Flaccid Paraplegic due to TM July 1985 @ age 12

  2. #12
    Here's the contact information to visit with Dr. Shi. Mention the Working 2 Walk Presentation in reference to your questions.



    https://www.vet.purdue.edu/cpr/riyi/research_8.html

    Professor,
    Neuroscience and Biomedical Engineering
    Department of Basic Medical Sciences
    Center for Paralysis Research
    School of Veterinary Medicine
    Weldon School of Biomedical Engineering
    Purdue University
    West Lafayette, IN 47907-1244

    Tel: (765) 496-3018
    Fax: (765) 494-7605
    E-mail: riyi@purdue.edu

    Riyi Shi is a medical scientist specializing in uncovering the mechanisms of central nervous system trauma and diseases and instituting new treatments through innovative experimentation and pioneering new strategies in the field. His research contributions includes originating the use of double sucrose gap technique for recording action potential conduction, establishing the methods of neuronal membrane resealing by polyethelyne glycol (PEG), and identifying acrolein as a key pathological factor in spinal cord injury and multiple sclerosis. His research interests also include using nanotechnology to improve drug delivery to nervous tissue and incorporating biomedical engineering principles to enhance neuronal repair and diagnosis. This includes designing innovative scaffolds to enhance neuronal regeneration and using bioadhesives for neuronal tissue repair.

    This laboratory is committed to translate laboratory discoveries to novel and effective treatments for human patients of neuronal trauma and degenerative diseases. This is realized through multidisciplinary investigations using a combination of basic biology and engineering techniques. The goal of our research is to develop new therapies that can be rapidly translated into the clinic.

    Restoration of axonal conduction by potassium channel blocker:
    Most axons in the vertebral central nervous system are myelinated by oligodendrocytes. Myelin protects and insulates neuronal processes, enabling the fast, saltatory conduction unique to myelinated axons. It is well established that the increase of potassium channel activity is an important mechanism of conduction failure in spinal cord injury and multiple sclerosis. Suppressing aberrant potassium current by potassium channel blockade is an effective intervention for restoring signal conduction in demyelinated axons. Our lab has been involved in the original development of 4-aminopyridine, a well known potassium channel blocker that has seen recent clinical success as a treatment for multiple sclerosis symptoms. However, the narrow therapeutic range and the common side effects associated with its use limit the clinical application of 4-AP. In an effort to identify new compounds that could serve as viable alternatives to 4-AP, but perhaps with stronger effects and less side effects, We have identified several new compounds posses efficacy in restoring action potential conduction in injured axons. One of these potassium channel blockers, 4-AP-3-MeOH, was more potent than 4-AP. Furthermore, the derivative-rescued axons conduct electric impulses in a manner that is more like healthy axons than under 4-AP treatment. Therefore, these new derivatives are potential alternatives to 4-AP treatment in reversing conduction block in spinal cord injury and other demyelinating diseases. At the present time, 4-AP remains under study for use with spinal cord injury patients: blocking potassium channels remains a viable strategy in restoring axonal conduction and improving overall neurological function. Further studies of potassium blockade therapies for demyelinating diseases are warranted, as 4-AP has been approved for improving ambulatory ability in multiple sclerosis patients.

  3. #13
    Super Moderator Sue Pendleton's Avatar
    Join Date
    Jul 2001
    Location
    Wisconsin USA
    Posts
    10,998
    Quote Originally Posted by trekker6 View Post
    Sue, is he trying to make it available, is his testing complete? I can't get anyone to prescribe 4ap.
    Trekker, I think he had not started on animals yet when we were in Boston. The Center For Paralysis Research at Purdue is both well funded and has a reputation among veterinarians around the country for their work on dogs naturally injured. So anytime they get past mice or rats they send out a notice and vets can then let dog owners know that their dog can be included in a clinical trial that normally is free to very low cost and often gets dogs walking using a K-9 cart for support. Outside of those trials where the dogs go home afterwards most dogs paralyzed by an accident or disc problem are euthanized.

    Have you spoken to your insurance provider about Ampyra? Most pharmacists that say it's not available are actually saying your insurance won't pay for it unless you have MS. Try talking to whoever covers your drugs and then explain to your doctor how the prescription needs to be handled. It is a high cost medication and the FDA has been cracking down on the pharmaceutical companies that try to or do push their meds off label without separate trials. So Acorda hired an outside company to handle their marketing especially of the prescriptions that they give out at a reduced cost and not even discussing off label use is allowed. I spent awhile figuring this out but it does seem to come down to your insurance provider and what hoops they want you to jump through to get it. My BC/BS is making me have their MS Department sign off on my needing it. Good luck dealing with the system.
    Last edited by Sue Pendleton; 07-10-2014 at 05:03 AM.
    Courage doesn't always roar. Sometimes courage is the quiet voice at the end of the day saying, "I will try again tomorrow."

    Disclaimer: Answers, suggestions, and/or comments do not constitute medical advice expressed or implied and are based solely on my experiences as a SCI patient. Please consult your attending physician for medical advise and treatment. In the event of a medical emergency please call 911.

  4. #14
    I spoke with Dr. Shi at Working 2 Walk and he told me that one of his ideas to improve the delivery of potassium channel blockers (I'm not sure if this includes PEG or not) was to combine the oral form of PCBs with magnesium. After you swallow the pill, you would literally wear a magnet at the site of your injury for an hour or two, to get the magnesium-laced PCB's to be more drawn towards your injury, rather than just randomly float through the blood stream. I asked him about direct surgical delivery of PCBs or doing something similar to a baclofen pump to constantly deliver it, and he said he is not a fan of either of those ideas because the potential health complications from having a surgery or pump in your body is something nobody needs. This makes me wonder if he wants to come up with a non-surgical way of delivering PEG.

    There is currently a clinical trial underway for incomplete SCI combining 4-AP and locomotor training:
    http://clinicaltrials.gov/ct2/show/N...+injury&rank=1

    In my opinion, in order to maximize the effects of PCBs they must be combined with intensive physical therapy or exercise. If no demand is placed on the body, there is no reason for axons to conduct action potentials, and the effects of the PCBs are wasted. Dr. Shi talked more in depth about that when I spoke to him at W2W, saying that if you take a PCB and just sit there, you're going to experience very minimal, if any effects from it.
    I think that is one of the big reasons 4-AP was approved for MS, because in the MS trial, the ability to walk was one of the requirements. If you give something to people who can already walk something that makes them feel stronger and have more energy, what are they going to do? Walk more! That in and of itself is physical training and very likely had an effect on the outcomes of the trial.

  5. #15
    Quote Originally Posted by tomsonite View Post

    There is currently a clinical trial underway for incomplete SCI combining 4-AP and locomotor training:
    http://clinicaltrials.gov/ct2/show/N...+injury&rank=1
    I took part in the initial 4-AP Clinical Trial and later, the NRN Clinical Trial. I don't know for sure if I was taking the placebo or 4-AP but I suspect it was the 4-AP because I had better sexual function. It did not improve my walking or spasms at all.

    The NRN program did not improve my walking at all. I'm not very optimistic that the combination will be effective but you never know.

  6. #16
    Quote Originally Posted by Jim View Post
    I took part in the initial 4-AP Clinical Trial and later, the NRN Clinical Trial. I don't know for sure if I was taking the placebo or 4-AP but I suspect it was the 4-AP because I had better sexual function. It did not improve my walking or spasms at all.

    The NRN program did not improve my walking at all. I'm not very optimistic that the combination will be effective but you never know.
    I've met a few people who's walking didn't improve due to the NRN, but have had success with other methods. Because the NRN is research based, has a very strict algorithm for how to set up a session and thus its ability to be tailored to individuals is limited.

    My hypothesis is that those whose walking would improve because of the NRN, would have their walking improve even further if it was NRN + 4AP. Others would need much more individually tailored training programs.

  7. #17
    Quote Originally Posted by tomsonite View Post
    I spoke with Dr. Shi at Working 2 Walk and he told me that one of his ideas to improve the delivery of potassium channel blockers (I'm not sure if this includes PEG or not) was to combine the oral form of PCBs with magnesium. After you swallow the pill, you would literally wear a magnet at the site of your injury for an hour or two, to get the magnesium-laced PCB's to be more drawn towards your injury, rather than just randomly float through the blood stream. I asked him about direct surgical delivery of PCBs or doing something similar to a baclofen pump to constantly deliver it, and he said he is not a fan of either of those ideas because the potential health complications from having a surgery or pump in your body is something nobody needs. This makes me wonder if he wants to come up with a non-surgical way of delivering PEG.

    There is currently a clinical trial underway for incomplete SCI combining 4-AP and locomotor training:
    http://clinicaltrials.gov/ct2/show/N...+injury&rank=1

    In my opinion, in order to maximize the effects of PCBs they must be combined with intensive physical therapy or exercise. If no demand is placed on the body, there is no reason for axons to conduct action potentials, and the effects of the PCBs are wasted. Dr. Shi talked more in depth about that when I spoke to him at W2W, saying that if you take a PCB and just sit there, you're going to experience very minimal, if any effects from it.
    I think that is one of the big reasons 4-AP was approved for MS, because in the MS trial, the ability to walk was one of the requirements. If you give something to people who can already walk something that makes them feel stronger and have more energy, what are they going to do? Walk more! That in and of itself is physical training and very likely had an effect on the outcomes of the trial.
    Would there be a way to incorporate the use of a DREADD receptor then? Perhaps the long way around, but potentially the non-surgical way...

  8. #18
    I wonder if a DREADD (which I hadn't heard of until you brought it up, so I just looked up what it was and thus have a very cursory understanding) could be engineered to bind to a site in the body, then be activated to hold on to another molecule passing through the blood stream? I'm not sure if that's even possible but it looks like a DREADD could be engineered to be a bridge of sorts, i.e. engineer one end to bind to a de-myelinated axon, and the other end to bind to PEG or an engineered PCB. It looks like I've got my reading agenda for the weekend...

  9. #19
    Super Moderator Sue Pendleton's Avatar
    Join Date
    Jul 2001
    Location
    Wisconsin USA
    Posts
    10,998
    I was still doing 5 day a week outpatient PT when I was in the 4-AP phase 2 trial for incomplete SCI. I went from a few shallow knee bends between the parallel bars to about 20 real knee bends almost immediately. After the study was unblinded I had definitely been able to tell which time I was taking the drug and taking the placebo. I found after the trial that the longer I was on it the more return I got but never to the point of more than a few steps in the bars without any braces. But having my quads score 5/5 made my life much easier as far as standing transfers went. Now that the spouse is getting older and my neurons are wearing out it is time to get back on the drug and into a real exercise program. So yes, I think of all those I knew who were in the trials who were happy with the results were either still in an exercise/PT program or able to walk some and it allowed more walking or walking in warmer weather. But Acorda was looking at walking improvement and spasticity as end points and with a fairly short trial I think they would have needed a much larger group and skip spasticity control to get it approved for incomplete SCI.
    Courage doesn't always roar. Sometimes courage is the quiet voice at the end of the day saying, "I will try again tomorrow."

    Disclaimer: Answers, suggestions, and/or comments do not constitute medical advice expressed or implied and are based solely on my experiences as a SCI patient. Please consult your attending physician for medical advise and treatment. In the event of a medical emergency please call 911.

  10. #20
    Thanks for your input everyone, and Grammy, thanks for Dr Shi's contact information.
    If I'm not mistaken, the newer, better 4AP-3-MeOH is not yet in clinical use?

Similar Threads

  1. Replies: 1
    Last Post: 01-11-2009, 01:02 AM
  2. Who's on Calcium Channel Blockers?
    By Lee555 in forum New SCI
    Replies: 2
    Last Post: 01-11-2008, 09:07 PM
  3. Replies: 0
    Last Post: 10-06-2003, 06:45 PM
  4. Replies: 0
    Last Post: 01-20-2003, 09:06 AM
  5. Replies: 0
    Last Post: 07-21-2002, 06:02 AM

Posting Permissions

  • You may not post new threads
  • You may not post replies
  • You may not post attachments
  • You may not edit your posts
  •