Page 57 of 63 FirstFirst ... 74748495051525354555657585960616263 LastLast
Results 561 to 570 of 623

Thread: Clinical Trials

  1. #561
    Yea, the statement shouldn't be as definitive as they made it but doctors, researchers that I've spoken to all agree that continued returns after 6 months-1 year (especially in the case of the most severe, complete injuries) is really the exception rather than the rule.

  2. #562
    The National Acute Spinal Cord Injury Study suggests that a majority of people do continue to recover some function after one year but the recovery is less than during the first year.

    In a poll of people on CareCure (see http://sci.rutgers.edu/forum/poll.ph...lts&pollid=141), about two-thirds of people recovered some function a year or more after spinal cord injury.

    Wise.

  3. #563
    Dear Dr. Wise,

    Did you hear anything about the matrix Laminin? A group of researchers in pittsburgh are trying to put laminin into damaged spinal cords. This matrix should be benefical for regenerating neurons!
    Last edited by KK11; 03-07-2013 at 07:51 AM.

  4. #564
    Quote Originally Posted by Wise Young View Post
    The National Acute Spinal Cord Injury Study suggests that a majority of people do continue to recover some function after one year but the recovery is less than during the first year.

    In a poll of people on CareCure (see http://sci.rutgers.edu/forum/poll.ph...lts&pollid=141), about two-thirds of people recovered some function a year or more after spinal cord injury.

    Wise.
    I don't know about the NASCIS but obviously the carecure poll doesn't provide any information on the extent of the gains nor the extent of initial injury. I just know with an injury like my own, nothing like that will happen...and therefore don't care much to hear about spontaneous recovery and don't think it has really much relevance to a discussion of therapies restoring function. Limited natural recovery and return is why we need a cure, after all...
    Last edited by ay2012; 03-08-2013 at 03:23 PM.

  5. #565
    Quote Originally Posted by ay2012 View Post
    The molecule, known as NgR(310)ecto-Fc, binds to all three ligands – Nogo-A, myelin-associated glycoprotein (MAG) and OMgp – effectively blocking the body’s natural inhibitors of axonal sprouting and regeneration. Resumption of axonal growth leads to the potential for enhanced recovery, Cassidy explained.
    Hmmmm, where else have we seen evidence of this?

  6. #566
    Quote Originally Posted by KK11 View Post
    Dear Dr. Wise,

    Did you hear anything about the matrix Laminin? A group of researchers in pittsburgh are trying to put laminin into damaged spinal cords. This matrix should be benefical for regenerating neurons!
    Laminin is a protein that is produced by fibroblasts (skin cells) and is usually not present (except in small quantities around blood vessels) in the central nervous system. Axons grow alacritously on laminin but they tend to become spoiled and not want to grow in the central nervous system after having spent time growing on laminin. We use laminin all the time in tissue culture.

    Laminin and collagen are both basement membrane proteins. Collagen comprises significant portion of skin and scar tissue. Collagen is also frequently used to coat cell culture dishes. Cells adhere to collagen and laminin. Axons like to grow in collagen as well. Like laminin, collagen is very attractive to axons but once they grow on collagen, they don't like to grow in the central nervous system environment.

    Actually, many years ago in 1995, I remember Jerry Silver showing a beautiful demonstration of the tendency of axons to avoid chondroitin-6-proteoglycans (CSPG) after they have grown on laminin. He made culture dish that were coated with strips of laminin alternating with strips of CSPG. He then plated dorsal root ganglion neurons onto the culture dish. Neurons that landed on CSPG strips will send out axons. The axons grow on CSPG but when they crossed over to the laminin strips, they did not grow back onto the CSPG strips. Neurons that landed on laminin also sent out axons but they seldom crossed over into CSPG strips.

    Based on this, one might think that it would not be a good idea to put laminin or collagen into the injury site. Axons might grow into the injury site but will not grow out again in the spinal cord to complete their journey. In other words, you don't want to make the "bridge" across the injury site to be so attractive that they don't want to leave the bridge.

    Wise.

  7. #567
    Quote Originally Posted by ay2012 View Post
    I don't know about the NASCIS but obviously the carecure poll doesn't provide any information on the extent of the gains nor the extent of initial injury. I just know with an injury like my own, nothing like that will happen...and therefore don't care much to hear about spontaneous recovery and don't think it has really much relevance to a discussion of therapies restoring function. Limited natural recovery and return is why we need a cure, after all...
    ay2012,

    For many years, doctors assumed that people do not recover from spinal cord injury. In the 1970's and 1980's, doctors were telling patients that they will never recover any function and they should not even try. Even in the 1990's, some doctors were saying this to patients. Now we of course know that a large majority (90%) of people with severe spinal cord injury can and do recover substantial function if they have sacral sparing (i.e. some anal sensation or ability to contract their anal sphincter voluntarily). Over 60% of people who have spinal cord injury have sacral sparing, i.e. incomplete. Yet, you still see most scientific articles starting with false statements that claim that recovery does not occur after spinal cord injury.

    Many studies suggest that some people with so-called "complete" spinal cord do recover substantial function at a year or more after spinal cord injury. It is true that not many do so but nevertheless it can and does happen about 10% of the time. Of course, you have lots of naysayers who claim that the original examination was not carefully done. But, most of the time, these claims are being made by doctors who do not see many patients for long times after spinal cord injury. That is part of the problem. Most of the initial examinations are done by emergency room doctors and surgeons who see the patient during the first several weeks after injury while most of the long-term followup examinations are done by physiatrists who assess the patients many weeks, months, or years after injury.

    I have been studying spinal cord injury since 1979, both in animals and people. I have seen people with "complete" spinal cord injury recover substantial and sometimes many years after injury. It is rare but it happens. Let me cite three examples of people that I knew personally: Carey Erickson, Pat Rummersfeld, and Christopher Reeve. Carey was one of the first patients that I treated with high dose methylprednisolone in 1980. He had a C4/5 injury with patch of sensation on his left leg and did not have sacral sparing. Over 3 years after his injury, he recovered ability to walk to the point where you could not tell him from normal. He worked for me for 7 years from 1983 to 1990. Pat also had a spinal cord injury and was apparently paralyzed for several years after a horrendous accident where he damaged his spinal cord over 4-5 segments. I am not sure whether he had sacral sparing or not but he was given no chance by any doctor to recover any function, much less walking or running. He now runs marathons and is a triathlete. People of course know the story of Christopher Reeve. Many doctors have confirmed that he was a ASIA A complete spinal cord injury at C3. He did not recover walking but he did get some function back more than a year after injury. At about 2 years after injury, Christopher went from ASIA A to C when he recovered anal sensation and found that he could move his left index finger and move his legs slightly. He also recovered sensation in most of his body, down to mid-thigh level.

    What is such delayed recovery due to? I am not sure but we cannot rule out regeneration as a mechanism.

    Wise.

  8. #568
    Quote Originally Posted by Wise Young View Post
    ay2012,

    For many years, doctors assumed that people do not recover from spinal cord injury. In the 1970's and 1980's, doctors were telling patients that they will never recover any function and they should not even try. Even in the 1990's, some doctors were saying this to patients. Now we of course know that a large majority (90%) of people with severe spinal cord injury can and do recover substantial function if they have sacral sparing (i.e. some anal sensation or ability to contract their anal sphincter voluntarily). Over 60% of people who have spinal cord injury have sacral sparing, i.e. incomplete. Yet, you still see most scientific articles starting with false statements that claim that recovery does not occur after spinal cord injury.

    Many studies suggest that some people with so-called "complete" spinal cord do recover substantial function at a year or more after spinal cord injury. It is true that not many do so but nevertheless it can and does happen about 10% of the time. Of course, you have lots of naysayers who claim that the original examination was not carefully done. But, most of the time, these claims are being made by doctors who do not see many patients for long times after spinal cord injury. That is part of the problem. Most of the initial examinations are done by emergency room doctors and surgeons who see the patient during the first several weeks after injury while most of the long-term followup examinations are done by physiatrists who assess the patients many weeks, months, or years after injury.

    I have been studying spinal cord injury since 1979, both in animals and people. I have seen people with "complete" spinal cord injury recover substantial and sometimes many years after injury. It is rare but it happens. Let me cite three examples of people that I knew personally: Carey Erickson, Pat Rummersfeld, and Christopher Reeve. Carey was one of the first patients that I treated with high dose methylprednisolone in 1980. He had a C4/5 injury with patch of sensation on his left leg and did not have sacral sparing. Over 3 years after his injury, he recovered ability to walk to the point where you could not tell him from normal. He worked for me for 7 years from 1983 to 1990. Pat also had a spinal cord injury and was apparently paralyzed for several years after a horrendous accident where he damaged his spinal cord over 4-5 segments. I am not sure whether he had sacral sparing or not but he was given no chance by any doctor to recover any function, much less walking or running. He now runs marathons and is a triathlete. People of course know the story of Christopher Reeve. Many doctors have confirmed that he was a ASIA A complete spinal cord injury at C3. He did not recover walking but he did get some function back more than a year after injury. At about 2 years after injury, Christopher went from ASIA A to C when he recovered anal sensation and found that he could move his left index finger and move his legs slightly. He also recovered sensation in most of his body, down to mid-thigh level.

    What is such delayed recovery due to? I am not sure but we cannot rule out regeneration as a mechanism.

    Wise.
    Fair enough, but from a (this) patient's perspective those are largely academic points. I don't want to bet my future on being one of the few like Carey Erickson or Pat Rummersfeld. Christopher Reeve of course DIED from complications related to his injury so whatever recovery he had was likely not all that enjoyable nor functional.
    I know you're just stating the facts, but again I say: in terms of "the cure" I don't want to talk about natural recovery. Unless I'm very very very very lucky or my expectations are so low that all I want is patchy sensation to return, natural recovery likely won't mean much to me. I want substantial functional return along a variety of dimensions and I want it with relative certainty (by this I mean, again, I don't want to simply wait years to see if I naturally recover). This is why I support the scientists looking for a cure.
    I'm sorry to labour on this point, but it makes me a bit emotional. You (obviously) don't know what it feels like to have people suggest you may naturally recover, or talk about how their son or daughter did, etc. when you lie awake every night in a hospital bed trying to move SOMETHING below your injury, to no avail. It's not for lack of trying...my injury is severe and I need something external to fix it.

  9. #569
    Quote Originally Posted by ay2012 View Post
    I'm guessing you wanted to post this:


    By Marie Powers
    Staff Writer

    Privately held Axerion Therapeutics Inc. hopes to translate two technologies exclusively licensed from Yale University into revolutionary therapeutics in a pair of indications – spinal cord injury (SCI) and Alzheimer’s disease (AD) – that have bedeviled biotechs and big pharmas, alike.
    With funding from Yale, Axerion was launched in late 2009 by the investment firm Scheer & Co. to develop and commercialize the platforms, discovered in the lab of neurology and neurobiology scientist Stephen Strittmatter at Yale School of Medicine. They include a Nogo decoy receptor for chronic SCI and related neurological diseases, and blockers of amyloid-beta oligomer binding to cellular prion protein (PrPc) on the cell surface of neurons as a therapeutic target for AD.
    The Nogo program was housed for a time at Biogen Idec Inc., of Weston, Mass., which returned the rights to Yale during a strategic reshuffling. Axerion snagged the asset shortly afterward, according to Sean Cassidy, the company’s chief financial officer.
    In April 2010, the Branford, Conn.-based start-up attracted $750,000 in seed funding from Connecticut Innovations and a grant from the National Institutes of Health (NIH) to develop the decoy receptor, a fusion protein that consists of the ectodomain of NgR1 fused to IgG1 . The molecule, known as NgR(310)ecto-Fc, binds to all three ligands – Nogo-A, myelin-associated glycoprotein (MAG) and OMgp – effectively blocking the body’s natural inhibitors of axonal sprouting and regeneration. Resumption of axonal growth leads to the potential for enhanced recovery, Cassidy explained.
    The company’s name is a play on the axonal regeneration program.
    “We’re the only therapeutic that has demonstrated the potential to work in a chronic setting,” Cassidy told BioWorld Today. Although biotechs such as Neuralstem Inc., Athersys Inc., Pluristem Therapeutics Inc. and StemCells Inc. have generated buzz in SCI, their approaches feature stem cell treatments.
    Targeting chronic SCI gives Axerion the ability to run smaller trials and to recruit more quickly. Recovery of function tapers off around six months following SCI and ceases altogether at about one year. At that point, “it’s easy to measure any recovery of motor function,” Cassidy pointed out. “You can actually take patients and utilize them as their own baseline.”
    The targeting of three inhibitory ligands is a key mechanistic reason for Axerion’s confidence in the Nogo program in chronic SCI. A Nogo antibody in development by Novartis AG in acute SCI and similar antibodies at GlaxoSmithKline plc targeting amyotrophic lateral sclerosis and myelin-associated inhibitory pathways can only bind one inhibitor, explained George Maynard, Axerion’s vice president of preclinical development.
    “Blocking one inhibitor or single receptor is going to be less effective than our approach, with a receptor decoy that potentially will bind and then activate the effects of all three myelin-associated inhibitors,” he explained.
    The company needs about two years to complete preclinical safety studies and GMP manufacturing work before filing an investigational new drug (IND) application, according to Maynard. A Phase I proof-of-concept study could recruit ASIA-A, B and C patients and then “be data-driven in terms of how we refine the patient population going forward” into pivotal trials, he said. “We think we would be able to detect evidence of efficacy fairly quickly.”
    In December, Axerion was selected for participation in the NIH’s Bridging Interventional Development Gaps program, which will help the company to conserve capital by providing no-cost access to NIH therapeutic development contractor resources and supporting key activities, such as preclinical toxicity studies, required for the IND submission. The company plans to meet with the FDA and refine its clinical plan once it completes preclinical safety and pharmacokinetics studies.
    In April 2012, Axerion signed an exclusive sublicense with AstraZeneca plc’s Neuroscience Innovative Medicines Unit to conduct research, develop and commercialize the preclinical AD biologic. Axerion received an undisclosed up-front payment and is entitled to milestone payments, royalties on product sales and research and development funding during the collaboration period.
    Not only is AstraZeneca funding some of Axerion’s FTEs, but there’s a potential strategic payoff. While the big pharma is focused on a biologics approach to the PrPc pathway, Axerion retained global rights to a small-molecule approach and is actively seeking grant funding to advance its internal work, which avoids the amyloid-beta clearance and selectivity issues that have plagued other experimental AD compounds.
    “We’ve identified the key high-affinity binding sites on neurons for the toxic oligomeric form of amyloid-beta,” Maynard pointed out. “We’re blocking, specifically, that binding interaction.”
    With a handful of employees, the company has prevailed on about $2 million in seed funding in addition to government grants. Axerion hopes to move to the next level by raising a $15 million series A to finance the Nogo program through Phase I.
    Long term, the internal debate is not whether or not to partner, but at what stage.
    “We obviously made the decision to partner our biologics program early,” Cassidy said. “We could partner our small-molecule approach under the same pathway, or we may have the ability to develop that through the granting process.”
    With respect to the Nogo program, “once we start to see evidence the molecule is providing efficacy in humans, we would do market checks on the program,” he added.
    Is anyone know anything more about their rat successful NoGo Decoy approach and possible Human trial (timeline & now?) ?
    www.MiracleofWalk.com

    Miracles are not contrary to nature, but only contrary
    to what we know about nature
    Saint Augustine

  10. #570
    Quote Originally Posted by Wise Young View Post
    Laminin is a protein that is produced by fibroblasts (skin cells) and is usually not present (except in small quantities around blood vessels) in the central nervous system. Axons grow alacritously on laminin but they tend to become spoiled and not want to grow in the central nervous system after having spent time growing on laminin. We use laminin all the time in tissue culture.

    Laminin and collagen are both basement membrane proteins. Collagen comprises significant portion of skin and scar tissue. Collagen is also frequently used to coat cell culture dishes. Cells adhere to collagen and laminin. Axons like to grow in collagen as well. Like laminin, collagen is very attractive to axons but once they grow on collagen, they don't like to grow in the central nervous system environment.

    Actually, many years ago in 1995, I remember Jerry Silver showing a beautiful demonstration of the tendency of axons to avoid chondroitin-6-proteoglycans (CSPG) after they have grown on laminin. He made culture dish that were coated with strips of laminin alternating with strips of CSPG. He then plated dorsal root ganglion neurons onto the culture dish. Neurons that landed on CSPG strips will send out axons. The axons grow on CSPG but when they crossed over to the laminin strips, they did not grow back onto the CSPG strips. Neurons that landed on laminin also sent out axons but they seldom crossed over into CSPG strips.

    Based on this, one might think that it would not be a good idea to put laminin or collagen into the injury site. Axons might grow into the injury site but will not grow out again in the spinal cord to complete their journey. In other words, you don't want to make the "bridge" across the injury site to be so attractive that they don't want to leave the bridge.

    Wise.
    Thank you for the answer!

Similar Threads

  1. Secret Stem Cell Trial held in City
    By Wise Young in forum Cure
    Replies: 7
    Last Post: 12-04-2008, 10:48 AM
  2. Replies: 0
    Last Post: 11-08-2008, 08:49 AM
  3. Replies: 2
    Last Post: 04-18-2005, 10:46 AM
  4. Replies: 0
    Last Post: 06-03-2004, 02:42 PM
  5. Replies: 0
    Last Post: 06-03-2002, 06:33 PM

Posting Permissions

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