M E Cudkowicz

..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...

..While the majority of subjects tolerated higher dosages of NaPB, the lowest dose (9 g/day), was therapeutically efficient in improving histone acetylation levels...

..However, progress is being made in all of these regards...

..To test this hypothesis, the authors generated transgenic ALS mice with altered levels of glutathione peroxidase (GSHPx), the major soluble enzyme that detoxifies H2O2...

..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...

..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...

..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)...

..To determine if long-term topiramate therapy is safe and slows disease progression in patients with ALS...

..Thus, we conclude that the statistical method is not an appropriate measure of motor unit number in any disease associated with motor unit instability...

..Rates of FVC% and ALFRS decline, but not of MVIC-arm or MVIC-grip, were independent predictors of survival...

..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...

..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...

..We tested the hypothesis that this association correlates with functional changes in paraoxonase 1 (PON1, MIM 168820)...

..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...

..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...

..These data suggest that NaPB may not interfere with the pharmacologic action of riluzole in ALS patients...

..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...

..However, the decline in measures of function appears unchanged since then. These changes in natural history reflect improvements in symptomatic care of ALS...

..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...

..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...

..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...

..We present an overview of clinical trial methodology for ALS, including a summary rationale for target selection and challenges to ALS clinical research...

..Completed and ongoing clinical trials and the process of selecting drugs for clinical trials are presented...

..Riluzole is currently the only Food and Drug Administration-approved treatment for ALS, but its effect on survival is modest...

..Phenylbutyrate may therefore provide a novel therapeutic approach for the treatment of patients with ALS...

..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...

..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...

..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...

..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...

..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...

..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...

..This study investigates whether EIM could provide a new outcome measure for use in ALS clinical trials work...

..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)...

..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...

..These data suggest that combined minocycline and CoQ10 treatment may offer therapeutic benefit to patients suffering from HD...

..These are described and prioritized herein, and suggestions are offered for efficiently sifting through them...

..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...

..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...

..These findings indicate that circulating levels of MMP-9 are increased in AD and may contribute to disease pathology...

..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...

..CoQ10 appears to be safe and well tolerated, and several efficacy trials are planned...

..Abstract Not Provided. ..

..Secondary outcome measures will include ALSFRS-R, vital capacity, strength, and the long-term safety and tolerability of ceftriaxone in this population. ..

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..Secondary outcome measures include grip strength, forced vital capacity, the ALS functional rating scale, and the safety and tolerability of topiramate in this population. ..