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Thread: Mayo Clinic Changes Treatment for Spinal Cord Injury

  1. #21
    Quote Originally Posted by Leif View Post
    How did you find it valuable?
    I want to know exactly what the Level 1 Trauma Units like the Mayo Clinic is doing to spinal cord injury patients when they arrive there for treatment for their injury and what these Neurotrauma Surgeons are telling others to do when they call the Mayo Clinic for assistance in the United States. We have a right to know.

    Our Level 1 Neurotrauma Team Surgeons like at the Mayo Clinic wouldn't bother to do a search of Scandinavian practices for help in a crisis when that helicopter lands at THEIR hospital...(that is also known without even searching).
    Last edited by GRAMMY; 01-05-2012 at 03:13 AM.

  2. #22
    Quote Originally Posted by GRAMMY View Post
    I want to know exactly what the Level 1 Trauma Units like the Mayo Clinic is doing to spinal cord injury patients when they arrive there for treatment for their injury and what these Neurotrauma Surgeons are telling others to do when they call the Mayo Clinic for assistance in the United States. We have a right to know.

    Our Level 1 Neurotrauma Team Surgeons like at the Mayo Clinic wouldn't bother to do a search of Scandinavian practices for help in a crisis when that helicopter lands at THEIR hospital...(that is also known without even searching).
    I thought this article did a nice job of discussing the pros and cons of MP after SCI. After all these years the verdict is still not in.

    SPINE
    ORTHOPEDICS May 2010;33(5):327.
    High-Dose Methylprednisolone in Acute Spinal Cord Injuries: Proceed With Caution
    by Komal A. Pandya, PharmD; Kyle A. Weant, PharmD, BCPS; Aaron M. Cook, PharmD, BCPS
    The Bottom Line
    Published guidelines emphasize that there is insufficient data to support the use of methylprednisolone as a standard of care for the treatment of acute spinal cord injury.
    More research is needed on acute spinal cord injury to determine what agents, if any, improve outcomes.
    Practitioners should consider using high-dose methylprednisolone therapy for spinal cord injury patients while also weighing carefully the potential lack of benefit versus the consistently demonstrated risks of this therapy.

  3. #23

    steriods

    Just reading this article. My son is new SCI as of 12/6/11. The hospital he was at did give him steroids right away. Apparently they are not up to date with Mayo. The article did not say if giving steriods would hurt any recover results. Sure hope not.

  4. #24
    Quote Originally Posted by Mom15 View Post
    Just reading this article. My son is new SCI as of 12/6/11. The hospital he was at did give him steroids right away. Apparently they are not up to date with Mayo. The article did not say if giving steriods would hurt any recover results. Sure hope not.
    Mom15,

    Mayo Clinic did not say that high-dose methylprednisolone (MP) is not effective. They said that it is an option but not a standard of care. MP has always been an optional treatment because doctors have refused to acknowledge any treatment, including surgery, as a standard of care for spinal cord injury. If something is the standard of care, then a doctor can be sued for not giving it.

    In my opinion, the doctors who have been criticizing MP treatment for spinal cord injury have no data upon which to base their criticism. The data supporting the efficacy and safety of MP treatment for human spinal cord injury are very strong. The evidence suggesting that the treatment is ineffective or deleterious are weak. The following are the main clinical trials showing the MP is beneficial for acute spinal cord injury.

    • The Second National Acute Spinal Cord Injury Study (NASCIS II) published in 1990 by the New England Journal of Medicine showed that high dose MP improved recovery by about 20% (compared to placebo control) when the drug was started within 8 hours and continued for 24 hours after spinal cord injury.
    • A second study in Japan showed similar results.
    • A study in Sweden showed that people who have whiplash injuries [3] benefited from methylprednisolone therapy and had less sick time when treated within 8 hours after injury.
    • The third National Acute Spinal Cord Injury Study published in 1997 showed that a 48-hour course of MP is better than a 24-hour course of MP when the treatment is started between 3-8 hours after injury.

    There is no evidence from any randomized trial that the 24-hour course of MP causes aseptic necrosis of the joints, causes muscle degeneration, or has any other serious deleterious effects on people with spinal cord injury. NASCIS III did show that the 48-hour course of MP did cause a slight increase in severe pneumonias but this was readily treated with antibiotics. For that reason, early treatment with the 24-hour course is recommended while the 48-hour course of MP should be reserved only in cases when the drug cannot be started within 3 hours.

    I attach abstracts of the published papers for people who might be interested.


    Wise.

    References Cited
    1. Bracken MB, Shepard MJ, Collins WF, Holford TR, Young W, Baskin DS, Eisenberg HM, Flamm E, Leo-Summers L, Maroon J and et al. (1990). A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study. N Engl J Med 322: 1405-11. Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06510. Studies in animals indicate that methylprednisolone and naloxone are both potentially beneficial in acute spinal-cord injury, but whether any treatment is clinically effective remains uncertain. We evaluated the efficacy and safety of methylprednisolone and naloxone in a multicenter randomized, double-blind, placebo-controlled trial in patients with acute spinal-cord injury, 95 percent of whom were treated within 14 hours of injury. Methylprednisolone was given to 162 patients as a bolus of 30 mg per kilogram of body weight, followed by infusion at 5.4 mg per kilogram per hour for 23 hours. Naloxone was given to 154 patients as a bolus of 5.4 mg per kilogram, followed by infusion at 4.0 mg per kilogram per hour for 23 hours. Placebos were given to 171 patients by bolus and infusion. Motor and sensory functions were assessed by systematic neurological examination on admission and six weeks and six months after injury. After six months the patients who were treated with methylprednisolone within eight hours of their injury had significant improvement as compared with those given placebo in motor function (neurologic change scores of 16.0 and 11.2, respectively; P = 0.03) and sensation to pinprick (change scores of 11.4 and 6.6; P = 0.02) and touch (change scores, 8.9 and 4.3; P = 0.03). Benefit from methylprednisolone was seen in patients whose injuries were initially evaluated as neurologically complete, as well as in those believed to have incomplete lesions. The patients treated with naloxone, or with methylprednisolone more than eight hours after their injury, did not differ in their neurologic outcomes from those given placebo. Mortality and major morbidity were similar in all three groups. We conclude that in patients with acute spinal-cord injury, treatment with methylprednisolone in the dose used in this study improves neurologic recovery when the medication is given in the first eight hours. We also conclude that treatment with naloxone in the dose used in this study does not improve neurologic recovery after acute spinal-cord injury.
    2. Bracken MB, Shepard MJ, Collins WFJ, Holford TR, Baskin DS, Eisenberg HM, Flamm E, Leo SL, Maroon JC, Marshall LF, Perot P, Piepmeier J, Sonntag V, Wagner FC, Wilberger JE, Winn HR and Young W (1992). Methylprednisolone or naloxone treatment after acute spinal cord injury: 1-year follow-up data. Results of the second National Acute Spinal Cord Injury Study. J Neurosurg 76: 23-31. The 1-year follow-up data of a multicenter randomized controlled trial of methylprednisolone (30 mg/kg bolus and 5.4 mg/kg/hr for 23 hours) or naloxone (5.4 mg/kg bolus and 4.0 mg/kg/hr for 23 hours) treatment for acute spinal cord injury are reported and compared with placebo results. In patients treated with methylprednisolone within 8 hours of injury, increased recovery of neurological function was seen at 6 weeks and at 6 months and continued to be observed 1 year after injury. For motor function, this difference was statistically significant (p = 0.030), and was found in patients with total sensory and motor loss in the emergency room (p = 0.019) and in those with some preservation of motor and sensory function (p = 0.024). Naloxone-treated patients did not show significantly greater recovery. Patients treated after 8 hours of injury recovered less motor function if receiving methylprednisolone (p = 0.08) or naloxone (p = 0.10) as compared with those given placebo. Complication and mortality rates were similar in either group of treated patients as compared with the placebo group. The authors conclude that treatment with the study dose of methylprednisolone is indicated for acute spinal cord trauma, but only if it can be started within 8 hours of injury. Author-abstract.
    3. Pettersson K and Toolanen G (1998). High-dose methylprednisolone prevents extensive sick leave after whiplash injury. A prospective, randomized, double-blind study. Spine 23: 984-9. Department of Orthopaedics, Umea University, Sweden. STUDY DESIGN: A prospective, randomized, double-blind study comparing high-dose methylprednisolone with placebo. OBJECTIVES: To evaluate the efficacy of high-dose methylprednisolone when administered within 8 hours after whiplash injury. SUMMARY OF BACKGROUND DATA: Whiplash injury often results in chronic symptoms. The management of whiplash injuries is controversial, and pharmacologic therapy has received little evaluation. In recent reports, dysfunction of the central nervous system has been indicated in several cases. Methylprednisolone administered within 8 hours after the injury to patients with acute spinal cord injury has been demonstrated to improve the outcome. This procedure was also adopted in a randomized study of cases of whiplash injury in car accidents. METHODS: Forty patients, 22 men and 18 women with a mean age of 35 years (range, 19-65), were included in the study, 20 in each of two groups. They were treated for whiplash injury, which they had sustained in car accidents. The patients were enrolled if their diagnoses were complete and treatment had begun within 8 hours after injury. Disabling symptoms severe enough to prevent the patient from returning to work, number of sick days before and after injury, and sick-leave profile after injury were used as parameters for the evaluation of the effects of the treatment. Baseline demographic data were controlled for when statistical analysis had been performed. RESULTS: At the follow-up examination 6 months after initial treatment, there was a significant difference in disabling symptoms between the actively treated patients and the placebo group (P = 0.047), total number of sick days (P = 0.01), and sick-leave profile (P = 0.003). CONCLUSIONS: The results of this study indicate that acute treatment with high-dose methylprednisolone may be beneficial in preventing extensive sick leave after whiplash injury. However, the number of patients studied was small, and therefore further prospective, controlled studies are needed.
    4. Bracken MB and Holford TR (2002). Neurological and functional status 1 year after acute spinal cord injury: estimates of functional recovery in National Acute Spinal Cord Injury Study II from results modeled in National Acute Spinal Cord Injury Study III. J Neurosurg 96: 259-66. Department of Epidemiology, School of Medicine, and Graduate School, Yale University, New Haven, Connecticut 06520-8034, USA. michael.bracken@yale.edu. OBJECT: In the second National Acute Spinal Cord Injury Study (NASCIS II) investigators evaluated several standard neurological parameters but not functional activity. This has led to questions concerning the clinical importance of the increase in neurological recovery observed following administration of methylprednisolone (MP) within 8 hours of acute spinal cord injury (SCI). The safety of the therapy has also been questioned. METHODS: Both neurological and functional recovery were assessed in NASCIS III, a trial that followed an almost identical protocol to NASCIS II. In the current analysis locally weighted scatterplot smoothing (LOESS) nonparametric regression is used to model the extent of recovery in the Functional Independence Measure (FIM) that is predicted by improvement in the NASCIS/American Spinal Cord Injury Association motor scores that were documented in NASCIS III 1 year after SCI, and the models are applied to the extent of motor recovery demonstrated in NASCIS II. The models predict improvement in FIM that would be expected from the motor function recovery observed in NASCIS II. Estimates are provided overall and for patients with complete and incomplete neurological loss at time of injury. The authors review recent evidence obtained from randomized studies documenting adverse effects that may result from high-dose MP therapy. The relationship between motor function and FIM is strongly nonlinear and dependent on initial level of injury and degree of injury severity. In the best statistical model, the expanded motor score could be used to explain 77.2% of the variability in the FIM. Based on the mean MP-related 3.6-unit improvement in the motor score for patients with complete injuries and 7.3 for those with incomplete injuries owed to MP in NASCIS II, 18.6% of patients would improve six or more FIM points and 9% nine or more points, respectively. In those with complete neurological injury, the mean motor improvement of 3.6 predicted that 63.9% of the patients would improve three or more FIM points and 12.1% six or more points to a maximum of eight points. Of those with incomplete neurological injury, a 7.3 mean improvement in motor function predicted that 27.4% would gain six or more FIM points and that 21% would gain nine or more points to a maximum of 15 points. Analysis of the current best evidence from SCI and other randomized surgical trials in which high-dose MP has been administered provides no grounds for concern about commonly studied adverse effects. CONCLUSIONS: The extent of MP therapy-related motor function recovery observed in NASCIS II predicted clinically important recovery in the FIM. Reasons to be cautious with regard to this prediction include the lack of robustness in statistical modeling, some loss of validity in the FIM, and considerable heterogeneity in the SCI population. Whatever functional activity is ascribed to high-dose MP therapy, it is does not appear to be associated with risk of adverse outcomes.
    5. Bracken MB, Shepard MJ, Holford TR, Leo-Summers L, Aldrich EF, Fazl M, Fehlings M, Herr DL, Hitchon PW, Marshall LF, Nockels RP, Pascale V, Perot PL, Jr., Piepmeier J, Sonntag VK, Wagner F, Wilberger JE, Winn HR and Young W (1997). Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury. Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial. National Acute Spinal Cord Injury Study. Jama 277: 1597-604. OBJECTIVE: To compare the efficacy of methylprednisolone administered for 24 hours with methyprednisolone administered for 48 hours or tirilazad mesylate administered for 48 hours in patients with acute spinal cord injury. DESIGN: Double-blind, randomized clinical trial. SETTING: Sixteen acute spinal cord injury centers in North America. PATIENTS: A total of 499 patients with acute spinal cord injury diagnosed in National Acute Spinal Cord Injury Study (NASCIS) centers within 8 hours of injury. INTERVENTION: All patients received an intravenous bolus of methylprednisolone (30 mg/kg) before randomization. Patients in the 24-hour regimen group (n=166) received a methylprednisolone infusion of 5.4 mg/kg per hour for 24 hours, those in the 48-hour regimen group (n=167) received a methylprednisolone infusion of 5.4 mg/kg per hour for 48 hours, and those in the tirilazad group (n=166) received a 2.5 mg/kg bolus infusion of tirilazad mesylate every 6 hours for 48 hours. MAIN OUTCOME MEASURES: Motor function change between initial presentation and at 6 weeks and 6 months after injury, and change in Functional Independence Measure (FIM) assessed at 6 weeks and 6 months. RESULTS: Compared with patients treated with methylprednisolone for 24 hours, those treated with methylprednisolone for 48 hours showed improved motor recovery at 6 weeks (P=.09) and 6 months (P=.07) after injury. The effect of the 48-hour methylprednisolone regimen was significant at 6 weeks (P=.04) and 6 months (P=.01) among patients whose therapy was initiated 3 to 8 hours after injury. Patients who received the 48-hour regimen and who started treatment at 3 to 8 hours were more likely to improve 1 full neurologic grade (P=.03) at 6 months, to show more improvement in 6-month FIM (P=.08), and to have more severe sepsis and severe pneumonia than patients in the 24-hour methylprednisolone group and the tirilazad group, but other complications and mortality (P=.97) were similar. Patients treated with tirilazad for 48 hours showed motor recovery rates equivalent to patients who received methylprednisolone for 24 hours. CONCLUSIONS: Patients with acute spinal cord injury who receive methylprednisolone within 3 hours of injury should be maintained on the treatment regimen for 24 hours. When methylprednisolone is initiated 3 to 8 hours after injury, patients should be maintained on steroid therapy for 48 hours.
    6. Bracken MB (2002). Steroids for acute spinal cord injury. Cochrane Database Syst Rev CD001046. Department of Epidemiology and Public Health, Yale School of Medicine, 60 College street, Box 20834, New Haven, Connecticut, 06520-8034, USA. brackenmb@maspo3.mas.yale.edu. BACKGROUND: Acute spinal cord injury is a devastating condition typically affecting young people with a preponderance being male. Steroid treatment in the early hours of the injury is aimed at reducing the extent of permanent paralysis during the rest of the patient's life. OBJECTIVES: To review randomized trials of steroids for acute spinal cord injury. SEARCH STRATEGY: The review draws on the search strategy developed by the Cochrane Injuries Group. In addition, files of the National Acute Spinal Cord Injury Study have been reviewed and a Medline search conducted. SELECTION CRITERIA: All published or unpublished randomized controlled trials of steroid treatment for acute spinal cord injury in any language. DATA COLLECTION AND ANALYSIS: Data have been abstracted from original trial reports. For the NASCIS, Japanese and French trials, additional data (e.g. SDs) have been obtained from the original authors. MAIN RESULTS: There are few trials in this area of medical care. Only one steroid has been extensively studied, methylprednisolone sodium succinate, which has been shown to improve neurologic outcome up to one year post injury if administered within eight hours of injury and in a dose regimen of: bolus 30mg/kg administered over 15 minutes with a maintenance infusion of 5.4 mg/kg per hour infused for 23 hours. The initial North American trial was replicated in a Japanese trial but not in the one from France. Data has been obtained from the latter studies to permit appropriate meta-analysis of all three trials. This analysis indicates significant recovery in motor function after methylprednisolone therapy when administration commences within eight hours of injury. A more recent trial indicates that if methylprednisolone therapy is given for an additional 24 hours (for a total of 48 hours), additional improvement in motor neurologic function and functional status is observed. This is particularly observed if treatment cannot be started until between three to eight hours after injury. The same methylprednisolone therapy has been found effective in whiplash injuries and a modified regimen found to improve recovery after surgery for lumbar disc disease. REVIEWER'S CONCLUSIONS: High dose methylprednisolone steroid therapy is the only pharmacological therapy shown to have efficacy in a Phase Three randomized trial when it can be administered within eight hours of injury. A recent trial indicates additional benefit by extending the maintenance dose from 24 to 48 hours if start of treatment must be delayed to between three and eight hours after injury. There is an urgent need for more randomized trials of pharmacological therapy for acute spinal cord injury.
    Last edited by Wise Young; 01-07-2012 at 01:31 AM.

  5. #25
    Very interesting. Thank you again, Wise.

  6. #26
    Senior Member brucec's Avatar
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    Quote Originally Posted by Wise Young View Post
    Pelican,

    It is not true that the FDA does not have jurisdiction over Department of Defense (DoD) trials. DoD clinical trials are required to get IND (initial new drug/device application) for clinical trials. I have been sitting in various meetings involving clinical trials for the DoD and they work closely with the FDA to get permission for trials.

    Wise.
    I'm sure DoD can get permission alot easier than a company or organization
    We must reject the idea that every time a law's broken, society is guilty rather than the lawbreaker. It is time to restore the American precept that each individual is accountable for his actions.
    Ronald Reagan

  7. #27
    Quote Originally Posted by jsilver View Post
    I thought this article did a nice job of discussing the pros and cons of MP after SCI. After all these years the verdict is still not in.

    SPINE
    ORTHOPEDICS May 2010;33(5):327.
    High-Dose Methylprednisolone in Acute Spinal Cord Injuries: Proceed With Caution
    by Komal A. Pandya, PharmD; Kyle A. Weant, PharmD, BCPS; Aaron M. Cook, PharmD, BCPS
    The Bottom Line
    Published guidelines emphasize that there is insufficient data to support the use of methylprednisolone as a standard of care for the treatment of acute spinal cord injury.
    More research is needed on acute spinal cord injury to determine what agents, if any, improve outcomes.
    Practitioners should consider using high-dose methylprednisolone therapy for spinal cord injury patients while also weighing carefully the potential lack of benefit versus the consistently demonstrated risks of this therapy.
    Jerry,

    Please, there are no consistently demonstrated risks of the 24-hour course of MP. Hundreds of thousands, if not millions of people, have taken this dose of MP in the past 20 years. If there were any "consistently demonstrated risks of this therapy", there should be hundreds of papers reporting such risks. Except for one controlled clinical trial described below, none has shown any significant risk of the 24-hour MP treatment.

    One single-center clinical trial randomized 106 patients to four treatment groups (nimodipine, methylprednisolone, nimodipine+methylprednisolone, and placebo), showing no significant difference between the four treatment groups [1]. The trial was fatally flawed because it has too few patients in each treatment group and did not stratify between complete and incomplete spinal cord injuries. Therefore, even small differences in the ratios of complete and incomplete injuries amongst the treatment groups could result in significant differences in recovery and complications unrelated to treatments. There have been no other randomized trial that indicate that MP is ineffective and causes significant complications.

    This trial contrasts sharply with three double-blind randomized multicenter clinical trials involving over 1000 patients showing significant improvements of motor and sensory scores between MP treatments and other treatments (including placebo, naloxone, tirilazad mesylate). All these trials balanced complete and incomplete, as well as para- and tetraplegic patients, amongst the treatment groups and did stratified analyses. None of the trials show significant deleterious effects of the 24-hour course of MP.

    Incidentally, the claims that the NASCIS II and NASCIS III trials involved post-hoc analyses are false. A planned hypothesis in both trials is that earlier therapy would be better than late therapy. Therefore, both trials compared early treatment against delayed therapy. As pointed out above, careful balancing of the randomization and stratification of the analyses by complete and incomplete spinal cord injuries are crucial because the people with incomplete injuries recover much more than people with complete injuries. Even a slight imbalance in ratios of complete and incomplete patients in the treatment groups can result in big changes in recovery and complications. Both NASCIS II and NASCIS III were funded by NIH, peer-reviewed by the most rigorous reviewers, and published in the best available journals.

    The article that you cite is not credible.

    Wise.



    1. Pointillart V, Petitjean ME, Wiart L, Vital JM, Lassie P, Thicoipe M and Dabadie P (2000). Pharmacological therapy of spinal cord injury during the acute phase. Spinal Cord 38: 71-6. Unite de Pathologie Rachidienne, Hopital Pellegrin, Bordeaux, France. STUDY DESIGN: Prospective, randomized clinical trial. SETTING: France. OBJECTIVES: To evaluate the safety and effect on neurological outcome of nimodipine, methylprednisolone, or both versus no medical treatment in spinal-cord injury during the acute phase. METHOD: One hundred and six patients who had spinal trauma (including 48 with paraplegia and 58 with tetraplegia) were randomly separated into four groups: M=methylprednisolone (30 mg x kg(-1) over 1 h, followed by 5.4 mg x kg(-1) x h(-1) for 23 h), N=nimodipine (0.015 mg x kg(-1) x h(-1) for 2 h followed by 0.03 mg x kg(-1)h(-1) for 7 days), MN (both agents) or P (neither medication). Neurological assessment (ASIA score) was performed by a blinded senior neurologist before treatment and at 1-year follow-up. Early spinal decompression and stabilization was performed as soon as possible after injury. RESULTS: One hundred patients were reassessed at 1 year. Neurological improvement was seen in each group (P<0.0001), however no additional neurological benefit from treatment was observed. Infectious complications occurred more often in patients treated with M. Early surgery (49 patients underwent surgery within 8 h of their accident) did not influence the neurological outcome. The only predictor of the latter was the extent of the spinal injury (complete or incomplete lesion). CONCLUSION: The present study confirms the absence of benefit of pharmacological therapy in this indication. Because of the paucity of clinical studies that demonstrate the efficacy of pharmacological treatment in spinal injury during the acute phase, systematic use of pharmaceutical agents should be reconsidered.
    Last edited by Wise Young; 01-07-2012 at 01:22 AM.

  8. #28
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    This is very interesting. I doctor at Mayo Clinic. I will be sending some emails today. If I remember right, there is some connection with some of the docs. at Mayo and Acorda. I will let you know if I get anything back on this upcoming trial.

  9. #29
    I wish I had gotten MP after my injury in 1986. I was injured in Charlottesville, VA and UVA (level 1 trauma) was not using it yet. It is my understanding that they started using it as part of their protocol in the late 80's and they still use it today.

    What really angers and saddens me it that nothing else to help new or old injuries has come along since.

  10. #30
    Quote Originally Posted by momo3 View Post
    This is very interesting. I doctor at Mayo Clinic. I will be sending some emails today. If I remember right, there is some connection with some of the docs. at Mayo and Acorda. I will let you know if I get anything back on this upcoming trial.
    You mean for the proposed nerve regeneration trial for the brain? Or a rumor now started by conjecture in #7, 8, and 9? No particular SCI trial has been announced yet for Mayo, we were just discussing research being done.

    Acorda is affiliated with Mayo (Dr. Moses Rodgriguez). They're working on M.S. with signaling molecules in white matter cells with rHlgM22 for CNS myelin (a binding to oligodendrocytes). Acorda plans to file an IND the first half of this year and a Phase 1 in the 2nd half of 2012. For now this is for MS...

    Acorda incidentally is working on AC105 for acute stage SCI. A drug that can reduce lesion size and save functional losses. This could potentially be a very important drug and revolutionize the standard of care for acute SCI neurotrauma.

    http://mayoresearch.mayo.edu/mayo/re...ion_update.cfm
    Last edited by GRAMMY; 01-10-2012 at 03:25 PM.

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