M E Cudkowicz

Summary

Affiliation: Massachusetts General Hospital
Country: USA

Publications

  1. pmc Oral repeated-dose toxicity studies of coenzyme Q10 in beagle dogs
    Padmaja Yerramilli-Rao
    Neurology Clinical Trials Unit, Massachusetts General Hospital, 13th Street, Building 149, Room 2274, Charlestown, MA 02129, USA
    Int J Toxicol 31:58-69. 2012
  2. doi request reprint Dexpramipexole versus placebo for patients with amyotrophic lateral sclerosis (EMPOWER): a randomised, double-blind, phase 3 trial
    Merit E Cudkowicz
    Massachusetts General Hospital, Neurology Clinical Research Institute, Charlestown, MA, USA Electronic address
    Lancet Neurol 12:1059-67. 2013
  3. doi request reprint Toward more efficient clinical trials for amyotrophic lateral sclerosis
    Merit E Cudkowicz
    Massachusetts General Hospital, Boston, Massachusetts, USA
    Amyotroph Lateral Scler 11:259-65. 2010
  4. doi request reprint Arimoclomol at dosages up to 300 mg/day is well tolerated and safe in amyotrophic lateral sclerosis
    Merit E Cudkowicz
    Neurology Clinical Trials Unit, Massachusetts General Hospital, 13th Street, Charlestown, MA 02129, USA
    Muscle Nerve 38:837-44. 2008
  5. doi request reprint Phase 2 study of sodium phenylbutyrate in ALS
    Merit E Cudkowicz
    Massachusetts General Hospital, Neurology Clinical Trials Unit, 13th Street, Charlestown, MA 02129, USA
    Amyotroph Lateral Scler 10:99-106. 2009
  6. ncbi request reprint Trial of celecoxib in amyotrophic lateral sclerosis
    Merit E Cudkowicz
    Neurology Clinical Trials Unit, Massachusetts General Hospital, Harvard Medical School, Boston, 02172, USA
    Ann Neurol 60:22-31. 2006
  7. pmc Measures and markers in amyotrophic lateral sclerosis
    Merit Cudkowicz
    Neurology Clinical Trial Unit, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    NeuroRx 1:273-83. 2004
  8. ncbi request reprint A randomized, placebo-controlled trial of topiramate in amyotrophic lateral sclerosis
    M E Cudkowicz
    Neurology Clinical Trials Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    Neurology 61:456-64. 2003
  9. ncbi request reprint Survival in transgenic ALS mice does not vary with CNS glutathione peroxidase activity
    M E Cudkowicz
    Day Neuromuscular Laboratory, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA
    Neurology 59:729-34. 2002
  10. ncbi request reprint Revised statistical motor unit number estimation in the Celecoxib/ALS trial
    J M Shefner
    Department of Neurology, SUNY Upstate Medical University, Syracuse, New York 13210, USA
    Muscle Nerve 35:228-34. 2007

Research Grants

  1. DOUBLE BLIND STUDY OF MINOCYCLINE IN HD
    Merit Cudkowicz; Fiscal Year: 2007
  2. Clinical Trial of Ceftriaxone in ALS
    Merit Cudkowicz; Fiscal Year: 2007
  3. Coenzyme Q10 in Huntington's Disease
    Merit Cudkowicz; Fiscal Year: 2007
  4. Coenzyme Q10 in Huntington's Disease
    Merit Cudkowicz; Fiscal Year: 2005
  5. Metabolomic Signatures in ALS
    Merit Cudkowicz; Fiscal Year: 2005
  6. CLINICAL TRIAL OF TOPIRAMATE IN ALS
    Merit Cudkowicz; Fiscal Year: 2003

Detail Information

Publications45

  1. pmc Oral repeated-dose toxicity studies of coenzyme Q10 in beagle dogs
    Padmaja Yerramilli-Rao
    Neurology Clinical Trials Unit, Massachusetts General Hospital, 13th Street, Building 149, Room 2274, Charlestown, MA 02129, USA
    Int J Toxicol 31:58-69. 2012
    ..Behaviors, blood chemistries, and detailed histopathology were normal. No deaths occurred. These results support the use of a 2400 mg/d dosage of CoQ₁₀ in human clinical trials...
  2. doi request reprint Dexpramipexole versus placebo for patients with amyotrophic lateral sclerosis (EMPOWER): a randomised, double-blind, phase 3 trial
    Merit E Cudkowicz
    Massachusetts General Hospital, Neurology Clinical Research Institute, Charlestown, MA, USA Electronic address
    Lancet Neurol 12:1059-67. 2013
    ..We aimed to assess efficacy and safety of dexpramipexole in a phase 3 trial of patients with familial or sporadic disease...
  3. doi request reprint Toward more efficient clinical trials for amyotrophic lateral sclerosis
    Merit E Cudkowicz
    Massachusetts General Hospital, Boston, Massachusetts, USA
    Amyotroph Lateral Scler 11:259-65. 2010
    ..Here we summarize our current thinking about phase II design options and the potential benefits of a clinical trial network for phase II trials in ALS...
  4. doi request reprint Arimoclomol at dosages up to 300 mg/day is well tolerated and safe in amyotrophic lateral sclerosis
    Merit E Cudkowicz
    Neurology Clinical Trials Unit, Massachusetts General Hospital, 13th Street, Charlestown, MA 02129, USA
    Muscle Nerve 38:837-44. 2008
    ..Arimoclomol CSF levels increased with dose. Arimoclomol was shown to be safe, and it crosses the blood-brain barrier. Serum pharmacokinetic profiles support dosing of three times per day. An efficacy study in ALS is planned...
  5. doi request reprint Phase 2 study of sodium phenylbutyrate in ALS
    Merit E Cudkowicz
    Massachusetts General Hospital, Neurology Clinical Trials Unit, 13th Street, Charlestown, MA 02129, USA
    Amyotroph Lateral Scler 10:99-106. 2009
    ..While the majority of subjects tolerated higher dosages of NaPB, the lowest dose (9 g/day), was therapeutically efficient in improving histone acetylation levels...
  6. ncbi request reprint Trial of celecoxib in amyotrophic lateral sclerosis
    Merit E Cudkowicz
    Neurology Clinical Trials Unit, Massachusetts General Hospital, Harvard Medical School, Boston, 02172, USA
    Ann Neurol 60:22-31. 2006
    ..To determine whether chronic treatment with celecoxib, a cyclooxygenase-2 inhibitor that has been shown to be beneficial in preclinical testing, is safe and effective in amyotrophic lateral sclerosis (ALS)...
  7. pmc Measures and markers in amyotrophic lateral sclerosis
    Merit Cudkowicz
    Neurology Clinical Trial Unit, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    NeuroRx 1:273-83. 2004
    ..However, progress is being made in all of these regards...
  8. ncbi request reprint A randomized, placebo-controlled trial of topiramate in amyotrophic lateral sclerosis
    M E Cudkowicz
    Neurology Clinical Trials Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    Neurology 61:456-64. 2003
    ..To determine if long-term topiramate therapy is safe and slows disease progression in patients with ALS...
  9. ncbi request reprint Survival in transgenic ALS mice does not vary with CNS glutathione peroxidase activity
    M E Cudkowicz
    Day Neuromuscular Laboratory, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA
    Neurology 59:729-34. 2002
    ..To test this hypothesis, the authors generated transgenic ALS mice with altered levels of glutathione peroxidase (GSHPx), the major soluble enzyme that detoxifies H2O2...
  10. ncbi request reprint Revised statistical motor unit number estimation in the Celecoxib/ALS trial
    J M Shefner
    Department of Neurology, SUNY Upstate Medical University, Syracuse, New York 13210, USA
    Muscle Nerve 35:228-34. 2007
    ..Thus, we conclude that the statistical method is not an appropriate measure of motor unit number in any disease associated with motor unit instability...
  11. ncbi request reprint Functional outcome measures as clinical trial endpoints in ALS
    B J Traynor
    Neurology Clinical Trials Unit, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA
    Neurology 63:1933-5. 2004
    ..Rates of FVC% and ALFRS decline, but not of MVIC-arm or MVIC-grip, were independent predictors of survival...
  12. ncbi request reprint Effect of neurophilin ligands on motor units in mice with SOD1 ALS mutations
    J M Shefner
    Department of Neurology, Upstate Medical University, Syracuse, NY 13210, USA
    Neurology 57:1857-61. 2001
    ..Mice with trangenes that express mutations in the gene for cytosolic copper/zinc superoxide dismutase (SOD1) develop motor neuron degeneration resembling human ALS. Neurophilin ligands are small molecules that promote neurite outgrowth...
  13. ncbi request reprint A clinical trial of creatine in ALS
    J M Shefner
    Department of Neurology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13104, USA
    Neurology 63:1656-61. 2004
    ..Creatine stabilizes the mitochondrial transition pore, and is important in mitochondrial ATP production. In a transgenic mouse model of ALS, administration of creatine prolongs survival and preserves motor function and motor neurons...
  14. doi request reprint Paraoxonase 1 (PON1) organophosphate hydrolysis is not reduced in ALS
    A M Wills
    Day Neuromuscular Research Laboratory, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
    Neurology 70:929-34. 2008
    ..We tested the hypothesis that this association correlates with functional changes in paraoxonase 1 (PON1, MIM 168820)...
  15. pmc Phase II trial of CoQ10 for ALS finds insufficient evidence to justify phase III
    Petra Kaufmann
    Department of Neurology, Clinical Coordinating Center, Columbia University, New York, NY 10032, USA
    Ann Neurol 66:235-44. 2009
    ..Our aims were to choose between two high doses of CoQ10 for ALS, and to determine if it merits testing in a Phase III clinical trial...
  16. ncbi request reprint The use of statistical MUNE in a multicenter clinical trial
    J M Shefner
    Department of Neurology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, New York 13210, USA
    Muscle Nerve 30:463-9. 2004
    ..Thus, MUNE can be used reliably as an outcome measure in multicenter clinical trials; specific remedies are suggested for the difficulties encountered in this study...
  17. ncbi request reprint Clinical trials in amyotrophic lateral sclerosis: the tenuous past and the promising future
    Rabia B Choudry
    Neurology Clinical Trials Unit, Department of Neurology, Massachusetts General Hospital, 55 Fruit Street, GRB 1256, Boston, MA 02114, USA
    J Clin Pharmacol 45:1334-44. 2005
    ..Completed and ongoing clinical trials and the process of selecting drugs for clinical trials are presented...
  18. doi request reprint The natural history of ALS is changing: improved survival
    Muddasir Qureshi
    Neurology Clinical Trials Unit, Massachusetts General Hospital, Harvard Medical School, 13th Street, Boston, MA 02129, USA
    Amyotroph Lateral Scler 10:324-31. 2009
    ..However, the decline in measures of function appears unchanged since then. These changes in natural history reflect improvements in symptomatic care of ALS...
  19. ncbi request reprint Increased incidence of deep venous thrombosis in ALS
    M Muddasir Qureshi
    Neurology Clinical Trials Unit, Department of Neurology, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Neurology 68:76-7. 2007
  20. doi request reprint Medications and laboratory parameters as prognostic factors in amyotrophic lateral sclerosis
    Muddasir Qureshi
    Neurology Clinical Trials Unit, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
    Amyotroph Lateral Scler 9:369-74. 2008
    ..035). We conclude that aspirin or NSAID use may shorten survival in ALS, while calcium use may prolong survival. Our results support a need to further explore the role of neuroinflammation in the pathogenesis of ALS...
  21. doi request reprint Is it too soon for mesenchymal stem cell trials in people with ALS?
    Irina Badayan
    Neurology Clinical Trials Unit, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
    Amyotroph Lateral Scler 9:321-2. 2008
    ..A pilot study of intraspinal injections of mesenchymal stem cells (MSC) was conducted in 9 participants. We review this paper, the rationale, preclinical data and study design...
  22. doi request reprint Lyme disease serology in amyotrophic lateral sclerosis
    Muddasir Qureshi
    Neurology Clinical Trials Unit, Massachusetts General Hospital, Harvard Medical School, 13th Street, Building 149, Room 2274, Charlestown, Massachusetts 02129, USA
    Muscle Nerve 40:626-8. 2009
    ..97%) had confirmed past immunoreactive infection. Two of these patients received ceftriaxone for 1 month without clinical improvement. Lyme disease was rare in 414 patients with ALS and is not likely to be causative...
  23. ncbi request reprint Translating preclinical insights into effective human trials in ALS
    Allitia B DiBernardo
    Department of Neurology, Massachusetts General Hospital, Boston, MA 02129, USA
    Biochim Biophys Acta 1762:1139-49. 2006
    ..We present an overview of clinical trial methodology for ALS, including a summary rationale for target selection and challenges to ALS clinical research...
  24. doi request reprint Combined riluzole and sodium phenylbutyrate therapy in transgenic amyotrophic lateral sclerosis mice
    Steven J Del Signore
    Department of Neurology, Boston University School of Medicine, Boston, MA, USA
    Amyotroph Lateral Scler 10:85-94. 2009
    ..These data suggest that NaPB may not interfere with the pharmacologic action of riluzole in ALS patients...
  25. doi request reprint Clinical significance in the change of decline in ALSFRS-R
    Carmen Castrillo-Viguera
    Massachusetts General Hospital, Charlestown, 02129, USA
    Amyotroph Lateral Scler 11:178-80. 2010
    ..This survey demonstrated that the majority of clinicians and clinical researchers surveyed believe that a therapy that resulted in a change of 20% or greater in the slope of the ALSFRS-R would be clinically meaningful...
  26. ncbi request reprint Neuroprotective agents for clinical trials in ALS: a systematic assessment
    B J Traynor
    Neurology Clinical Trials Unit, Department of Neurology, Massachusetts General Hospital, Boston, USA
    Neurology 67:20-7. 2006
    ..Riluzole is currently the only Food and Drug Administration-approved treatment for ALS, but its effect on survival is modest...
  27. ncbi request reprint Sodium phenylbutyrate prolongs survival and regulates expression of anti-apoptotic genes in transgenic amyotrophic lateral sclerosis mice
    Hoon Ryu
    Geriatric Research Education and Clinical Center, Bedford VA Medical Center, Bedford, Massachusetts, USA
    J Neurochem 93:1087-98. 2005
    ..Phenylbutyrate may therefore provide a novel therapeutic approach for the treatment of patients with ALS...
  28. ncbi request reprint Analysis of factors that modify susceptibility and rate of progression in amyotrophic lateral sclerosis (ALS)
    M Muddasir Qureshi
    Neurology Clinical Trials Unit, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Amyotroph Lateral Scler 7:173-82. 2006
    ..Pertinent variables not associated with either causation or progression of ALS included physical activity, cigarette smoking and a history of physical trauma or other clinical disorders...
  29. ncbi request reprint Is erythropoietin a potential therapy for amyotrophic lateral sclerosis?
    Patrick O Butsch
    Department of Neurology, Neurology Clinical Trials Unit, Charlestown, MA 02129, USA
    Exp Neurol 206:11-5. 2007
  30. ncbi request reprint Dynamic markers of altered gait rhythm in amyotrophic lateral sclerosis
    J M Hausdorff
    Margret and H A Rey Laboratory for Nonlinear Dynamics in Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    J Appl Physiol (1985) 88:2045-53. 2000
    ..Moreover, a matrix of markers based on gait dynamics may be useful in characterizing certain pathologies of motor control and, possibly, in quantitatively monitoring disease progression and evaluating therapeutic interventions...
  31. ncbi request reprint The pharmacokinetics and pharmaco-dynamics of Procysteine in amyotrophic lateral sclerosis
    M E Cudkowicz
    Day Neuromuscular Research Laboratory, Massachusetts General Hospital, Charlestown 02114, USA
    Neurology 52:1492-4. 1999
    ..We found that oral administration of Procysteine was safe. Procysteine enters CSF after both IV and oral dosing and accumulates to significant levels in CSF. We also observed that CSF levels of glutathione fall dramatically with aging...
  32. ncbi request reprint Trimethoprim and sulfonamide-associated meningoencephalitis with MRI correlates
    H Blumenfeld
    Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA
    Neurology 46:556-8. 1996
    ..These MRI findings are important because they may aid in early diagnosis of this condition in the appropriate clinical setting. In addition, the white matter abnormalities suggest an encephalitic component in addition to the meningitis...
  33. ncbi request reprint Comparison of incremental with multipoint MUNE methods in transgenic ALS mice
    Jeremy M Shefner
    Department of Neurology, Upstate Medical University, 750 East Adams Street, Syracuse, New York 13210, USA
    Muscle Nerve 25:39-42. 2002
    ..71 for single motor unit action potential (SMUAP) amplitude and 0.95 for MUNE. In this model, therefore, both MUNE methods yield similar estimates and are equally effective at documenting progression of a lower motor neuron disorder...
  34. pmc Electrical impedance myography to assess outcome in amyotrophic lateral sclerosis clinical trials
    Seward B Rutkove
    Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    Clin Neurophysiol 118:2413-8. 2007
    ..This study investigates whether EIM could provide a new outcome measure for use in ALS clinical trials work...
  35. pmc Serum Nogo-A levels are not elevated in amyotrophic lateral sclerosis patients
    Noam Y Harel
    Department of Neurology, Yale University School of Medicine, New Haven, CT 06520 8018, USA
    Biomarkers 14:414-7. 2009
    ..0% vs 4.7%) displayed markedly elevated levels of Nogo-A. Additional study is required to determine the factors that lead to elevated Nogo-A levels in a subset of both ALS patients and healthy controls...
  36. doi request reprint Dextromethorphan plus ultra low-dose quinidine reduces pseudobulbar affect
    Erik P Pioro
    Section of ALS and Related Disorders, Department of Neurology, Neurological Institute, Cleveland Clinic, Cleveland, OH 44195, USA
    Ann Neurol 68:693-702. 2010
    ..To evaluate dextromethorphan combined with ultra low-dose quinidine (DMq) for treating pseudobulbar affect (PBA) in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS)...
  37. ncbi request reprint Ciliary neurotrophic factor genotype does not influence clinical phenotype in amyotrophic lateral sclerosis
    Ammar Al-Chalabi
    Department of Neurology, Academic Neuroscience Centre, Institute of Psychiatry, King s College London, London, United Kingdom
    Ann Neurol 54:130-4. 2003
    ..There was no difference in age of onset, clinical presentation, rate of progression, or disease duration for those with one or two copies of the null allele, excluding CNTF as a major disease modifier in ALS...
  38. ncbi request reprint Mitochondrial DNA from platelets of sporadic ALS patients restores normal respiratory functions in rho(0) cells
    Carl D Gajewski
    Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY 10021, USA
    Exp Neurol 179:229-35. 2003
    ..Therefore, we showed that mtDNA from platelets of ALS patients was able to restore normal respiratory function in rho(0) cells, suggesting that the presence of mtDNA mutations capable of affecting mitochondrial respiration was unlikely...
  39. pmc Proteomic profiling of cerebrospinal fluid identifies biomarkers for amyotrophic lateral sclerosis
    Srikanth Ranganathan
    Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    J Neurochem 95:1461-71. 2005
    ..We validated the SELDI-TOF-MS results for transthyretin and cystatin C by immunoblot and immunohistochemistry using commercially available antibodies. These findings identify a panel of CSF protein biomarkers for ALS...
  40. ncbi request reprint Combination therapy using minocycline and coenzyme Q10 in R6/2 transgenic Huntington's disease mice
    Edward C Stack
    Geriatric Research Education and Clinical Center, Bedford VA Medical Center, Bedford, MA 01730, USA
    Biochim Biophys Acta 1762:373-80. 2006
    ..These data suggest that combined minocycline and CoQ10 treatment may offer therapeutic benefit to patients suffering from HD...
  41. doi request reprint Scrutinizing enrollment in ALS clinical trials: room for improvement?
    Richard S Bedlack
    Duke University Medical Center, Durham, NC, USA
    Amyotroph Lateral Scler 9:257-65. 2008
    ..Patient factors' and 'physician factors' may play more important roles in influencing enrollment, as in oncology trials. Our survey data support this idea, and provide potential mechanisms for improving enrollment...
  42. ncbi request reprint Coenzyme Q treatment of neurodegenerative diseases of aging
    Wendy R Galpern
    National Institute of Neurological Disorders and Stroke, National Institutes of Health, 6001 Executive Blvd, Room 2225, Bethesda, MD 20892, USA
    Mitochondrion 7:S146-53. 2007
    ..CoQ10 appears to be safe and well tolerated, and several efficacy trials are planned...
  43. ncbi request reprint Increased plasma levels of matrix metalloproteinase-9 in patients with Alzheimer's disease
    Stefan Lorenzl
    Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 525 East 68th Street, Room F 610, New York, NY 10021, USA
    Neurochem Int 43:191-6. 2003
    ..These findings indicate that circulating levels of MMP-9 are increased in AD and may contribute to disease pathology...
  44. ncbi request reprint Emerging disease-modifying therapies for the treatment of motor neuron disease/amyotropic lateral sclerosis
    Richard S Bedlack
    Duke University Medical Center, Box 3333, Durham NC 27705, USA
    Expert Opin Emerg Drugs 12:229-52. 2007
    ..These are described and prioritized herein, and suggestions are offered for efficiently sifting through them...

Research Grants15

  1. DOUBLE BLIND STUDY OF MINOCYCLINE IN HD
    Merit Cudkowicz; Fiscal Year: 2007
    ..Abstract Not Provided. ..
  2. Clinical Trial of Ceftriaxone in ALS
    Merit Cudkowicz; Fiscal Year: 2007
    ..Secondary outcome measures will include ALSFRS-R, vital capacity, strength, and the long-term safety and tolerability of ceftriaxone in this population. ..
  3. Coenzyme Q10 in Huntington's Disease
    Merit Cudkowicz; Fiscal Year: 2007
    ..abstract_text> ..
  4. Coenzyme Q10 in Huntington's Disease
    Merit Cudkowicz; Fiscal Year: 2005
    ....
  5. Metabolomic Signatures in ALS
    Merit Cudkowicz; Fiscal Year: 2005
    ..abstract_text> ..
  6. CLINICAL TRIAL OF TOPIRAMATE IN ALS
    Merit Cudkowicz; Fiscal Year: 2003
    ..Secondary outcome measures include grip strength, forced vital capacity, the ALS functional rating scale, and the safety and tolerability of topiramate in this population. ..