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  • #46
    Dr. Jerry Silver Case Western University

    I'm privileged and honored to be able to talk to you about our work. I'm going to give you 2 slides that cover 30 years of work showing why regeneration is so hard, then some good news:

    Cajal put a knife into the back of a cat . . . axons retreat from the injury. He thought that the axons dried up and disappeared, but we know now that they just stay there indefinitely, waiting to be reawakened. Just a few can sprout, just a few and very slowly.

    There are molecules called proteoglycans that play a major in regeneration failure. In embroys there are places where axons don't grow normally, and it took decades to understand that those proteoglycans are involved in those places. In particular, there's one called NG2. They're thought to be a kind of glue, preventing the loss of what's been "learned" but also, unfortunately, acting as scars.

    What happens after injury, you have an inflammatory event in the center of the lesion, and macrophages show up, acting like little pacmen, driving the nerve fibers back. There are stem cells inside your cord, but they're trapped around the outside of the lesion. What Chase does is allow the nerve fibers to move within the lesion, but then when they get to the scar they're stuck.

    We decided to bypass the whole damn thing with a peripheral nerve graft.

    You can graft nerves and get them to go into the injury but you can't get them to come out

    So they looked at peripheral nerve bridging and adding Chase; in 2006 they fixed the extensor muscle in a hemisected cat's paw . . . okay, so if we can fix one muscle, can we fix another?

    Okay -- WATCH THIS VIDEO WHEN IT GETS POSTED. IT'S NOT POSSIBLE TO DO JUSTICE TO WHAT HE'S SAYING WITHOUT ACCESS TO THE IMAGES THAT HE'S REFERRING TO.

    When you make a lesion, nature creates what amounts to a giant net all around the spot . . .our idea was to add some Chase and see if we could penetrate that net. We only got about 10%. So we did a bridge of peripheral nerves and added Chase both above and below the lesion.

    They were focused on just one muscle and one graft. This paper is published in Nature in 2011. They were trying to cross this giant chasm of less than 1/2 of a millimiter.

    The respiratory rhythm neurons was their target.

    Return of diaphragm function, albeit very slow, is always patterned, never chaotic except for occasional skipped breaths as well as variations in amplitude between individual breaths. True functional regenration takes time!

    The quote above is directly from the slide . . . they waited for 8 weeks and didn't see recovery of regular breathing, got depressed, thought they had failed, put the rats away for further consideration. A month later somebody noticed that something had changed with the rats' breathing. They just hadn't waited long enough -- which is probably why there's an exclamation point on that slide.

    Importantly: cutting the graft completely eliminates returned activity in the diaphragm, proving that regeneration through the graft is critical for functional recovery.

    What about bladder/urinary/(and bowel/sexual!)function? Can our strategies be used to allow paralyzed animals and hopefully humans to urinate normally after sci?

    They did a t8 transection in a rat. Did the peripheral nerve graft, added the Chase, and waited. And waited. And they saw neurons growing.

    He's playing the sound of normal peeing in a not-paralyzed rat, and then in an anesthetized rat . .. God, I love science.

    What about chronic injury? They went one full year with the respiratory model in a rat. A single injection in the vicinity of the phrenic motor pool one year after c2 hemisection led to significant activity. This is very, very good news.

    Aaahhhh. I can't wait for the breakout session with this guy. Watch the video, soon to be up @ u2fp.org

    Comment


    • #47
      Dr. Keith Tansey, Director SCI Research and Restorative Neurology, Shepherd Center

      He has a PhD in spinal cord physiology, is board certified in neurology and sci medicine, serves on the board of directors for ASIA and the American Society for Neurorehabilitation, works at the SCI clinic at the Atlanta VA, the animal lab at Emory, and the human lab at the Shepherd Center

      Shepherd is the biggest neurorehab hospital in the us, member of SCI model systems and the neural recovery network, icu to outpatient rehab, and has a dedicated human researarch lab for sci called SCIL

      www.shepherd.org/research/spinal-cord-injury shows 38 projects enrolling patients and providing an online intake form for those who want to participate in research. Register into their database!

      Showing cross sections of two injured cords, one with a bunch of holes in it, like swiss cheese, and one with a dark lesion in the center. The swiss cheese one was a walker, the other completely paralyzed. Why?

      What's known is that you have sensory and motor neurons going to and from the brain; in completes, the circuitry fails completely. In incompletes, some remains. About half of "clinically complete" injuries have existing circuitry.

      So what is the neural circuitry for locomotor recovery after sci and how might we enhance that recovery? There is plasticity in sensory neurons that's sufficient for training stepping in animals with complete spinal cord transections.

      About to show a guy walking with a walker, a gait belt, and a trainer. He's had 2 weeks of lokomat training. It looks very hard. So they put him back into the lokomat . . . video shows him in the machine, looking very cmfortable. 12 weeks later, he's walking fairly normally with one laufband crutch.

      Who benefits from this kind of training? It depends on a lot of variables. Do you have voluntary bowel and bladder? Do you have spasticity? Do you walk at all? How long since your injury? Using these variables, they can do the math and predict how much walking speed will improve. Could they figure out how to get everybody to improve a lot, rather than just the people who met certain thresholds in those variables?

      So they did brain imaging to look at what was different in the brain between those who could improve and those who couldn't . . . then attached an electrode to the back of the reflex at the back of the knee of some subjects to look at (and stimulate) reflexes under various conditions, comparing uninjured, incompletes, and completes.

      What they saw was that it might be possible to sort of "work through" the hyper reflexes and calm them down over time. Re-training the existing nerves to do what they're meant to do.

      What they're doing now is stimulating posterior root muscle reflexes and classical soleus H-reflexes. . . . quads, hamstrings, triceps, and tibialis.

      Okay. The idea is to combine electronic stimulation with the sensory feedback that comes with lokomotor type exercise and see what happens.

      The lokomat becomes a scientific recording device that allows them to figure out how loading, gait speed and electric stimulation should best be combined. It lets them calibrate exactly how to, for example, fight tone so that walking becomes more normal. Showing that in a patient with bad clonus they can give the cord exactly how much stimulation it needs to one muscle group to overcome the one that is spazzing.

      We anticipate that an integrated use of transcutaneous spinal cord stimulation and locomotor training may promote faster or greater recover of locomotion . . .

      Break time.

      Comment


      • #48
        Originally posted by Christopher Paddon View Post
        Do you do the treadmill training at home?
        We have opened up a small gym with equipment we purchased for my son. We needed more space than was available at home so bought a small building to use. We have a rti 300 arm and leg stim bike, a homemade treadmill using air operated linear actuators to adjust the amount of weight bearing, standing frame glider, parallel bars, a tracksystem built into the ceiling for overground training, mats, Empi units, and more. We purchased all of the equipment for my son because insurance wouldn't pay because he is complete. All told we have 100K in equipment cost. We have part time employees with 1 PT and 5 physiologists who are very flexible with their time between us and a local gym. We have 5 sci people using the gym for free(we owned the equipment already) we ask that if they can they can help pay the physiologists. If we went to full time we could operate the gym for about 250K/yr. That cost would cover 10 people getting 4 4 4 split between the treadmill and other over ground therapies.

        Using a medical model therapy we would have to provide mental services, physician services, all PTs(most won't last a day on the treadmill), nursing services and many other unnecessary services driving the cost up by as much as 1,000%.

        Comment


        • #49
          Dr. John McDonald, Kennedy Krieger VP & Director

          The good news is that the nervous system is turning over all the time, cells are being born all the time. I started off at Washington University, where we were focused on acute injuries, but at KK we deal with people who live with paralysis. We have a sub-focus on pediatric sci and paralysis, and program designs for an individualized, lifelong, in home restoration therapy rehabilitation program.

          There's so much that's doable today, and everyone who needs it should have access to all of it.

          Agenda: The problem, Goals for restoration, Approaches to regeneration, Elictircal stimulation, Problem of reduction of activity, How activity is related to recovery of function, How to meet the cure halfway.

          Showing the mri of someone with a 20+ year injury. The cord dies from the inside out. At the center is the lesion and outside is "scar tissue" -- which used to be thought of as just dead stuff. Modern imaging shows that it's not. We've imaged a lot of cords of people who are Asia A, and the majority of them have plenty of surviving neurons.

          We want to reduce complications . . . 30% of sci require readmission to hospitals every year.

          John is showing his famous sketch from a 1999 Scientific American article; I'll try to find a copy to post in here.

          Regeneration strategy: optimize regeneration by normalizing levels of neural activity . . . using patterned neural activity that's fundamental to development and regeneration.

          Completely transect a rat at t8, implant a chip below the lesion, activate the peroneal nerve, expect to see enhanced indicies of regeneration . . . and we do.

          FES Locomotor Activity promotes progenitor cell generation (Li et al. Neurosci 2010)

          Okay . . . this means that electrical stim plus the right kind of activity is actually making new cells. And they can use markers to know if the cells are oligodendrocytes, astrocytes, neurons.

          Baclofen inhibits proliferation of cells . . . rats treated with baclofen get less functional recovery, too. We need to be careful about what drugs we're taking.

          Why use FES?
          -No pragmatic option for benefiting from physical activity with paralysis.
          -Benefits of moderate physical activity in paralysis are overwhelming and doable in the home.
          -Neural restoration is possible.
          -Regular, near normal input optimizes the nervous system for recovery.
          -Achieving significant, incremental improvements at any time following injury is possible.

          Showing video of an FES bike with a voiceover talking about the cellular benefits of FES biking. I guess I thought that everybody in this room and everybody reading this on CC has known this forever, but if not -- it's real. It's known.

          The issue we have is that there's a technological barrier to getting this into every single home where someone who needs it has access to it.

          Some clinical studies -- you can reverse physical deterioration, reduce complications, recover neurological function.

          Even very delayed recovery is possible: Chris Reeve.

          Went from Asia A to Asia C, 5 - 8 years recovery, 0 to 20% motor score recovery, went from 7 to 60% sensory recovery, had a 10-fold reduction in infections and use of antibiotics, improved his quality of life, enabling him to travel.

          Study Outcomes
          Most people lose function over a 3 year period
          RT subjects doubled muscle mass and halved fat mass and reduced spasticity
          RT subjects also reduced baclofen use for spasticity

          Asia conversion rates:
          A to BCD 33%
          B to CD 40%
          C to D 14%

          This is just the beginning of the curve; we're just learning how to manage all this, how to get this into peoples' homes.

          Comment


          • #50
            Panel: Caggiano, Silver, Tansey, McDonald

            All the guys from this morning's presentations are taking questions from the audience . . .

            Q: Basically, can you please hurry up with this Chase project?
            A: We really are trying very hard . . .

            Q: What kind of resources are you committing in terms of actual dollars? We need to get this into people . . enough with the rats.
            A: The Chase project studies cost hundreds of thousands of dollars, and if they're successful we move on to the more expensive parts
            A: (Silver) When basic science shows the kind of very promising result I showed a little while ago -- one injection, one week later, one year after injury -- there should be word of mouth, there should be -- I don't think money is the problem. If we're good enough to pass the peer review system, we should be able to get grants, we should need only 10 to 50s of thousands of dollars. If you put 15 million dollars into my lab, we can't go faster, we can just do the same thing a ta bigger scale. I will put my own grant money into this project, I don't need any more resources. I do need support to take the work from my lab to the clinic.

            Q: What shape would that support take, getting from the lab to the clinic?
            A: (Silver) Tony gave you an array of papers that showed that Chase has an effect; there's plenty of evidence out there . . . how do we flip the switch to get this to clinical trials . . . I don't know if there's a bottom line, but acorda's got to help. They've made some nice pure enzyme, and they're going to be looked around the wolrd All of you can talk to your physicians, some hospital somewhere is likely to try. It's so close.

            Q: Dr. Tansey, how does your work translate into outpatient services once they leave.
            A: These things run largely in parallel. Because we have ongoing research in so many areas, we have a high level of understanding of research by the clinical staff . . .the patients involved in care are able to enroll in studies. We have some patient populations seved better than others. An important part of translational research is the difficulty of getting from the lab to the human. It's great to see an example of something that works in an animal . . . how are they different? Then there's safety. Put me in a trial, I can't do any worse, yes you can, you can be in pain all day long for the rest of your life. Is there something between animal research and a clinical trial. Can we take 5 or 15 patients and see what kind of results you get. Do we really need millions of dollars to have multiple centers. Is there a rat equivalent for humans? The perception is that we aren't getting things to clinics with what we know . . . the reality is that the best thing you can do is work with a good therapist, take advantage of "practice-based evidence" -- the opposite of evidence-based practice.

            Q: I think it's ridiculous to suggest that funding is not a problem. If additional funding only allows you to test more rats, why not move to a chronic primate model and improve your end.
            A: Mark Tzyinsky is doing Chase with primates. Another 1/4 of a million per year in my lab
            Q: Why not go to a primate model first?
            A: They're very expensive ..
            Q: But doesn't that mean funding IS a problem?
            A: If there's a remarkable result, and people see it, and the NIH sees it, and grants are written, we shouldn't have to ask YOU. I think if the science is good, the money will come. We need to get our work peer-reviewed, we just have to earn it.
            Q: I have no doubt that everyone is here for the pure science . . . if you were only here to get rich, we'd all LOVE to see you get filthy rich . . .I think there's this "I'm not in this for the money" and I just want to say, I don't care if you are, as long as it goes faster.
            A: (McDonald) Another factor that it's a factor that a lot of young people are not coming into this field, because it's not that well-funded, and new ideas often come from new people. The shifting of NIH money toward this field has the effect of drawing talent.

            Q: Jack Kerouac's quote: those who are crazy enough to think they can change the world are generally the ones who do. About baclofen, how do you manage spasciticy if you don't take it?
            A: (McDonald) Baclofen often starts in the acute setting when spasticity is bad. But then the dosage gets raised and raised, and you have a new doctor who's not that versed in sci care, so you stay on it forever. And it's not really doing anything of value for you. We have other ways to deal with the issues it's supposed to deal with. The majority of people on baclofen are not getting the benefit they think they are, and it's very doable to get them off it. How do we optimize our patients.

            Q: In regards to FES for caudaequinal injuries . . . any new ideas? I did the FES bike for months and only got flickers.
            A: (McDonald)All CE injuries are not complete and nor are they all the same. There are things that can be done in order to move you forward, to get those muscles to contract --
            (Tansey) If you have nerve cells, you can use classic FES, if you don't, you can use another kind of stimulation -- and this is testable so we know which it is.

            Q: With regard to the locomotor plus stimulation training studies , what was the average duration of the studies?
            A: (Tansey) 3 times a week, 1 hour a day, for 3 months

            Comment


            • #51
              Thanks so very much Kate!! NRF, where are you located? Would love to be able to access your gym. I want to use FES but right now that means I must purchase something for my home or travel 90 miles one way. How does one buy a bike for themselves? I have a family of 5, one in college, self employed, etc. Is there funding oppourtunites for me?

              Comment


              • #52
                International Panel: Dennis Tesolat, Martin Codyre, Harvey

                Martin: Thanks to the organizers. This is my 3rd time, and I was injured 3 years ago . . . this is a unique event in the world & this is a great opportunity for us all. When I first came here, there was a father who had a child with an sci, and he said to the doctors: if I could help my daughter to regain function I'd cut off my own leg. Are you willing to do that, too? And the doctors said, no, sorry, I'm not committed at that level. Might be an apocryphal story, but it's about the level of commitment from everybody in this room.

                Here's my take, 3 years in . . . we've gone from the possibility of one trial to having competing trials, which is an incredibly positive thing to have happened in just three years, and we're looking at combination therapies. It's going to be very hard to them clinically tried . . . but I'm more positive about seeing therapies for us than I was at the beginning. CNS is in some senses the low hanging fruit. You can see outcomes very well, which is not the case with, for example, Parkinsons. Investors are interested.

                On the negative side, I've been really quite shocked to learn that there have been therapies, science in the papers, that might have helped some of us, including myself. If the Miami Project could say to me that hyperthermia doesn't work, I could take that, but just being in this situation because it was never given a rigorous trial is very hard. I'm also aware of the difficulties of bringing a product fully to market . . . $400 to 500 million to get to phase III trial in North America. That's frightening. Also the timing issues . . . 7 years to a saleable product, according the Geron representative who spoke yesterday. it's such a long, expensive road. Finally, the lack of true cohesiveness in the community has been quite shocking to me. We need to come together more at events like this.

                Harvey Sihota (from London): This is my first event and I've found it very eye opening . . . didn't sleep very much last night. Thinking about this panel and what we should say. My own background is in business and finance, so I'm daunted by the regulatory and financial barriers . . . are there creative solutions? Offshoring Phase I and II trials . . the fda is the fda is not a good answer for myself, and maybe not for you either. I'm interested in thinking outside the box.

                Dennis: This is the first time I've ever done a think like this over skype, so we'll see how it goes. I wanted to talk about our responsibility for a cure. Lots of people are wondering whose fault it is that we're still waiting. I want to talk about what we can do to support a cure. We can support the scientists, we can question organizations that talk about cure all the time. We can ask them hard questions . . . we started a campaign toward the Rick Hansen foundation, hoping they'd have a lot of things to share about how they're bringing us the cure.

                We didn't get an answer. We weren't trying to bring shame to anyone, we just wanted to know. I'm Canadian, so of course Rick Hansen was the person I looked to from the beginning. I think anybody who claims to be supporting a cure deserves our support -- but only if they're really doing it. What we need to do is

                Martin: Thanks to Dennis for raising that eloquent campaign online. We haven't really gotten a good answer yet, but we still want one. If anybody's listening, please help us out.

                Some major organizations that use the word "cure" in their promotional material:

                --Rick Hansen gets $25 million a year from federal funding and private donors, which they're using maybe 2 or 3 mill on restorative
                --CRDF raises $15 mill and spends about half on restorative research. They've got the solid brand, the best position to push for faster cures, and they're not taking full advantage of it.
                compare to MJ Fox, which raised $40, almost all of which went to Parkinsons research. Why does CRDF not do the same?
                --The Spinal Research Trust in the UK raises $3 mill per year, all of which goes to restorative research.
                --Wings for Life, basically the same kind of numbers.

                Q: from where I sit I see a lot of things wrong. Martin, you remember that 2 years ago at Wings for Life, I saw nothing for chronic injuries. I got mad. We see a lot of progress in the last few years, but it seems like about 30% of what we COULD have seen. We could be much further along toward a cure, which I define as getting out of the chair. We can't be happy just with bowel and bladder, not that we all don't want that. We have to take what we can in the short term but look toward the long. We need to push for a big change, or we'll all going to die in these chairs. Just start the clinical trials with Chase. We need to take the bull by the horn if we want to walk.

                A: Harvey -- two points. One is that everybody wants scientific rigor, but unfortunately it comes with politics and bureaucracy, which we need to get rid of. The other is the translation to the clinic. We don't see an appetite to create a product that we can use. Once in a while someone like inVivo comes along and tries to cross that valley. Our organization is interested in working with people like that.

                Martin: the model of relying on companies to get us from bench to bedside is problematic. If it takes $500 million to show that a therapy works, and the job of the fda is to make sure that it's done safely . . . but what that turns out to mean is a lot of nothing.

                Dennis: I think that what we're going to do is take up our own part of the job. What is it? If you're paralyzed and you have a part time job, your full time job is moving this along. If you're paralyzed and you have a full time job, your part time job is moving this along.

                Audience: a lot of us are speaking about hope, and that's awesome, but we need to talk about action. I hear that there's a lack of collaboration. I hear that it's not a function issue . . . I don't understand, that's very confusing. I heard Jerry Silver say "I'm fine." Well, I'm happy that you are fine, but I am not fine. You said that switching to a clinical trial is another story. Does that mean that you are not the one who is going to trigger a trial? Who is going to do that? I believe you and you seem to believe in what you do . . .I'm not here to criticize, but I want to know how we get well. Let's start with a goal: we want clinical trials in two years and manage toward it. Another side would be to manage the program as a whole . . . there's much more need for collaboration and an integral approach. How can this community take this forward? What is the next step?

                Jerry Silver: I think what you've already done, bringing scientists and companies together in one meeting is a huge step. You may not realize it, but having Tony and I sitting here next to each other is enormous. Acorda might be motivated to switch its focus . . .they're making a lot of money now, and I believe they may have enough to move this along. What we need is a kind of Wise Young to move Chase into trials . . . he spends an enormous amount of time traveling, selling, educating . . . that's why he's got a trial going and we don't.

                Martin: What you said about this particular event bringing people together is very, very true. I know of scientists and other people from business who've made similar connections. To be honest, I was flabbergasted that this doesn't happen ALL the time . . this is a catalyst for the future. Every time I've come here I've seen more and more.

                Audience: It does seem like we've got a lot of things going on that are not as coordinated as they could be . . . again, thanks to the organizers of this event for making this possible. It's fantastic. We need to form a community that allows all of us, USA and internationally, to choose a path and figure out what to support. There's competition in academia, in the corporate world -- we need to figure out creatively how to overcome it. So many things don't seem to build on one another. We need to form a group around this core at u2fp that does coordinated, cohesive advocacy.

                Tansey: It's all about money when it comes to healthcare payers. One thing that's hard is the difficulty of translation. First in Human Research is something you should look at . . . it's not just the fda that's the barrier. Think about assisted suicide; the idea there is that people can and should take autonomy in terms of their own lives. You could make the case that there would be an ethical way to create that option for spinal cord injury. You'd want to proceed very cautiously and ethically, but it bears examination.

                Martin: We will take that message with us to the Capitol. And here's another thing -- people in chairs are travelling all over the world, spending many thousands of dollars and NOT advancing science at all. We're already taking our lives and putting them into the hands of charlatans, so that decision has been made.

                ----------

                Just my own opinion, but that conversation was an astonishing instance of what u2fp has been after for the last 5 years . . . you need to imagine a half a dozen people sitting in a living room in suburban Minneapolis, dreaming that somehow it might be possible to create a space where people would see that advocacy matters, that it's doable for everybody, and most of all that it's probably the ONLY way we're ever going to get anywhere. It's a long way from there to here.
                Last edited by kate; 10-20-2011, 01:59 PM.

                Comment


                • #53
                  Originally posted by kate View Post
                  All the guys from this morning's presentations are taking questions from the audience . . .


                  Q: In regards to FES for caudaequinal injuries . . . any new ideas? I did the FES bike for months and only got flickers.
                  A: (McDonald)All CE injuries are not complete and nor are they all the same. There are things that can be done in order to move you forward, to get those muscles to contract --
                  (Tansey) If you have nerve cells, you can use classic FES, if you don't, you can use another kind of stimulation -- and this is testable so we know which it is.

                  Q: With regard to the locomotor plus stimulation training studies , what was the average duration of the studies?
                  A: (Tansey) 3 times a week, 1 hour a day, for 3 months
                  So they do not say what kind of stim is there other then FES? How do you get tested? Pretty vague answers

                  Comment


                  • #54
                    Heidi Marchand: FDA Ass't Commissioner for Special Heath Issues

                    I'm pleased to be here this afternoon; my first time speaking to this group. I'm somewhat surprised to see that it's as large as it is. I'm looking forward to talking with you individually.

                    Today's objectives:
                    1. understand the basic structure of the fda and the centers responsible for human therapeutic products

                    2. learn about fda's office of special health issues as a point of contact for patients and patient advocacy organizations

                    3. discover opportunities for patients and patient advocacy organizations to engage with fda

                    Health and Human Services is a cabinet-level department under the white house; the president appoints the head, who is confirmed by the congress and the senate. Within HHS is CDC, FDA, NIH, and Centers for medicare and Medicaid Services.

                    The FDA has 13,586 full time employees and a budget of $4B ($1.58 of that is in user fees)

                    NIH has 18, 784 FTEs and a budget of $32B

                    CDC has 9,753 FTEs and a budget of a measly $735M

                    Centers for Medicare and Medicaid has 4869 FTEs and a budget of $511B

                    The FDA's current leader is Obama appointee Margaret Hamburg, MD
                    She has 8 major offices reporting to her, one of which is the office of external affiars, which contains the office of special health issues.

                    Things get approved in one of 5 centers for drug development. Slide up of early '80s AIDS advocates in a big rally, holding a sign that said TIME ISN'T THE ONLY THING THE FDA IS KILLING. It got their attention, apparently, and let to the creation of the Office of Special Health Issues. This woman leads that group.

                    They have a group of patient liaisons and another of healthcare professional liaisons . . . what are the mechanisms for public input?

                    There are public advisory committee meetings, other public hearings, and individual communications. They get involved in trying to understand what the messages are with respect to biologics, drugs, and devices. They take what they learn and communicate with patient groups of all kinds . . . we could get on an email list that would feed us information about new drugs, safety, or initiatives the fda might be undertaking. The fda can't speak specifically about any individual product or company, because these matters are confidential.

                    They can't say why something is on hold, but they can say what sorts of things reviewers consider before something gets put on hold.

                    Drug development process . . . before humans can take it:
                    1. Quality assurance -- synthesis, purification, and stability
                    2. Non-Clinical -- two species (rodent plus something else) testing on starting dose, carcinogenicity

                    That part of things takes 2 or 3 years. Now you're into human trials, which is what the IND is for.

                    3. Phase 1,
                    4. Phase 2
                    5. Phase 3

                    Should have 1,500 patients, unless it's designated orphan or fast track. She's seen one trial that had only 150 patients. This takes 5 to 7 years. Then if everything goes well, you get an NDA filed to get FDA approval, which can take up to 20 years. And only 1 in 5 drugs makes it.

                    That last sentence seems wrong, but I'll check with her when we get to the panel. Even without it, this is pretty much blech.

                    Comment


                    • #55
                      Naha Bora, DOD, Director of Congressionally Directed medical Research Programs

                      CDMRP is part of a DOD group that targets research as directed by congress; since 1992, they've administered more than $6B in congressional appropriations.

                      Their goal is to foster high-risk, high-impact types of research. They assess the current state of science to accommodate rapid change. They use a two-tier review, where every proposal that passes scientific review gets a second review for mission relevance.

                      Grants have been given for several kinds of cancer, ms, and . . . sci.

                      The have partnerships with advocates, congress, researchers, and the DOD. There's a program cycle that goes like this

                      vision setting
                      Release of Program announcement
                      Pre application receipt
                      Pre application screening
                      invitation to submit
                      application receipt
                      peer review
                      programmatic review
                      commanding general approval
                      candidate award list
                      negotiations, contracting, regulatory, program issues
                      grant award

                      This guy oversees this entire process, and it's not just giving awards in the usa; 23 countries have been given grants from all over the planet.

                      We support awards at differing stages of careers
                      Support individuals and teams
                      Support innovation
                      Support Translation Research

                      They got started because of breast cancer advocates and have made extensive use of consumer reviewers.

                      How do consumers participate? They're in most of the steps I just named above. If you want to do this, there's an entire section dedicated to you at the website . . . which I'll get a link to in a minute.

                      The sci research program is relatively new. The mission is to fund innovative and interdisciplinary research and foster collaboration . . . getting to the clinic.

                      In 2011 they have 17 million dollars and plan to use it on about 11 awards.

                      Last year they gave grants for implementation research -- development of methods or approaches that would get things to the clinic, and to developing guidelines.

                      He's showing slides that detail how much money, where it's going or has gone, what area it's focused on. The peer review for the current grants will happen in January, a couple of months from now . . . you can volunteer to do this.

                      $750k for clinical trial in rehab
                      500k for investigaor initiated
                      400k for qualitative research award to help create studies that get researchers to understand issues better
                      750k for 2 or 3 principal investigators to colloborate with a t least 1 clinician and1 researcher

                      Kenneth Curley is the chair of the org, and he has an sci.
                      link

                      Comment


                      • #56
                        Panel: Heidi Marchand, Naba Bora

                        Q: What's fast track at the fda?
                        A: It's for those conditions that are life-threatening and have no other alternative therapies.
                        Q: Does it actually make things faster?
                        A: Well . . . the theory is that it would lower the development time, but not necessarily testing time. You would also want to request a priority review.

                        Q: Who has won the DOD grants in the past, and how do you follow up with them?
                        A: Everyone who gets an award must give an annual update, and those things are posted online. We track their spending quarterly. We now have every one of the 70-odd projects listed on our website.

                        Q: Heidi, I'm really disappointed that we didn't get to finish your presentation because a lot of us need to hear more about the fda . . . is there someone in your office who is focused on sci, and if so how do we track?
                        A: The person in my office is David Banks; he would be the one who could answer questions about topics unique to spinal cord. We have a patient representative program and we have 165 patient representatives, and that program is on our website if you want to apply. One of the things they would evaluate is your potential conflict of interest. You'd have to mess with a lot of paperwork, but it's a very worthwhile thing to do.

                        Q: Heidi, one thing we're always talking about is that a cure for sci will most likely involve combination therapies. How is the fda going to deal with that?
                        A: fda is not doing science, we're just evaluating it . . . one criteria that's always a point of some discussion is this: what's the endpoint that demonstrates success? What's a complete win, what's a partial win? The other question is how to design trials that involve more than one drug . . . patients do need to push and show willingness to see such things happen. There's also statistical testing; if you're going to talk to congress, ask what's in the prescription drug user re act 5

                        Q: As I see it today, we waste a lot of time trying to guess what will pass . . . can't we work together since the beginning, so that we don't have to have this back and forth, hold and release, wasted time.
                        A: Well, (she goes through the process as it now stands)
                        Q: No, no, the point is that what I've seen, for example, is the way the Geron thing went . . .
                        A: Well, here's the problem, there's information that goes back and forth as you go along. You're still learning in the preclinical and that information has to feed into what happens next. (she's saying that the process does kind of work that way now -- the structure is a set of gates, yes, but it's a collaborative set of gates)

                        Q: spilled my coffee, missed it . . . something about lost time due to employee turnover . . .
                        A: Naba says not in my group; Heidi says that regulatory affairs work is not on any college curriculum. It's always learn on the job, which means that people who know how to do this are rare. At DOD, they always hire outside consultants from universities so turnover isn't an issue. At fda, once you're on an IND, you're going to stay on the same project for the NDA.

                        Q: Naba, I'm one of the fundees, so I appreciate that you're here. I had a question about the IRB . . . we had to do that twice, once at our facility and once again in your organization.
                        A: We do that because it's the DOD and we do our own research. It's policy, and we know it's a burden of 2 or 3 months, but we're trying to streamline it.

                        Q: How does the fda sci specialist (David Banks) stay abreast of developments as they happen?
                        A: These are well-trained scientific, medical doctor, Ph.D component, go to lots of conferences . . . they're exposed to lots of information . . . I know that you can't always keep up with every single thing, but they're very well prepared for what they do.

                        Time for a break, then the last workshops. Oh, good.

                        Comment


                        • #57
                          Originally posted by momo3 View Post
                          Thanks so very much Kate!! NRF, where are you located? Would love to be able to access your gym. I want to use FES but right now that means I must purchase something for my home or travel 90 miles one way. How does one buy a bike for themselves? I have a family of 5, one in college, self employed, etc. Is there funding oppourtunites for me?
                          Sorry momo3 we're in Pennsylvania. RTI will sell direct, their phone # is 800-609-9166 but they're not cheap. I have heard of insurance coverage paying for them, the people at RTI can help try to get coverage.

                          Comment


                          • #58
                            Jerry Silver: I think what you've already done, bringing scientists and companies together in one meeting is a huge step. You may not realize it, but having Tony and I sitting here next to each other is enormous. Acorda might be motivated to switch its focus . . .they're making a lot of money now, and I believe they may have enough to move this along. What we need is a kind of Wise Young to move Chase into trials . . . he spends an enormous amount of time traveling, selling, educating . . . that's why he's got a trial going and we don't.
                            Why not a collaboration? China and the other SCI Networks were born like a platform to test therapies for chronic SCI, no?
                            -Ramps in buildings are necessary, but it would be usefull to have another ones for people (mind/heart).....

                            -Hoc non pereo habebo fortior me

                            Comment


                            • #59
                              Thanks nrf! My insurance is out. They pay for nothing! I guess I need to check back with RTI. FWI, didn't Dr. MacDonald help start this?

                              Comment


                              • #60
                                He was and is on the leading edge.

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