Search

Your search keyword '"Isaacson, S"' showing total 249 results
Start Over Author "Isaacson, S"
249 results on '"Isaacson, S"'

1. Improvement of non-motor symptoms with NE3107 adjunctive to Carbidopa / Levodopa in patients with Parkinson`s disease: A Phase 2A, placebo-controlled study

Author

Palumbo, J., primary, Reading, C., additional, Ahlem, C., additional, Osman, N., additional, Zhang, J., additional, Aldred, J., additional, Rodriguez, R., additional, Rivera-Rivera, E., additional, Isaacson, S., additional, Kumar, R., additional, Ellenbogen, A., additional, and Lang, A., additional

Published
2024
Full Text
View/download PDF

2. Continuous subcutaneous levodopa/carbidopa infusion (ND0612) for patients with Parkinson’s disease and motor fluctuations: A Phase 3, active-controlled study (BouNDless)

Author

Stocchi, F., primary, Espay, A., additional, Albanese, A., additional, Ellenbogen, A., additional, Ferreira, J.J., additional, Giladi, N., additional, Gurevich, T., additional, Hassin-Baer, S., additional, Hernandez-Vara, J., additional, Isaacson, S., additional, Kieburtz, K., additional, LeWitt, P., additional, Lopez-Manzanares, L., additional, Olanow, C.W., additional, Pahwa, R., additional, Poewe, W., additional, Sarva, H., additional, Yardeni, T., additional, Adar, L., additional, Lopes, N., additional, Sasson, N., additional, Case, R., additional, and Rascol, O., additional

Published
2024
Full Text
View/download PDF

4. Efficacy and Safety of AbobotulinumtoxinA (Dysport) for the Treatment of Hemiparesis in Adults With Upper Limb Spasticity Previously Treated With Botulinum Toxin: Subanalysis From a Phase 3 Randomized Controlled Trial

Author

Ayyoub, Z., Banach, M., Bensmail, D., Bentivoglio, A.R., Boyer, F.C., Brashear, A., Csanyi, A., Deltombe, T., Denes, Z., Edgley, S., Gul, F., Gracies, J.-M., Hedera, P., Isaacson, S., Isner-Horobeti, M.-E., Jech, R., Kaminska, A., Khatkova, S., Kocer, S., Lejeune, T., McAllister, P., Marciniak, C., Marque, P., O’Dell, M., Remy-Neris, O., Rubin, B., Rudzinska-Bar, M., Simpson, D., Skoromets, A., Timerbaeva, S.L., Valkovic, P., Vecchio, M., Walker, H., Wimmer, M., Marciniak, Christina, McAllister, Peter, Walker, Heather, Brashear, Allison, Edgley, Steven, Deltombe, Thierry, Khatkova, Svetlana, Banach, Marta, Gul, Fatma, Vilain, Claire, Picaut, Philippe, Grandoulier, Anne-Sophie, and Gracies, Jean-Michel

Published
2017
Full Text
View/download PDF

6. IncobotulinumtoxinA injections at intervals <10 weeks are effective and safe for cervical dystonia patients with inadequate benefit from standard intervals

Author

Comella, C., primary, Hauser, R., additional, Isaacson, S., additional, Truong, D., additional, Oguh, O., additional, Hui, J., additional, Molho, E., additional, Brodsky, M., additional, Furr-Stimming, E., additional, Comes, G., additional, Hast, M., additional, and Charles, D., additional

Published
2023
Full Text
View/download PDF

7. Treatment of cervical dystonia using shorter incobotulinumtoxinA injection intervals improves patient-reported outcomes in those with inadequate benefits from standard intervals

Author

Comella, C., primary, Isaacson, S., additional, Charles, D., additional, Truong, D., additional, Oguh, O., additional, Hui, J., additional, Molho, E., additional, Brodsky, M., additional, Furr-Stimming, E., additional, Comes, G., additional, Hast, M., additional, and Hauser, R., additional

Published
2023
Full Text
View/download PDF

10. Longitudinal clinical and biomarker characteristics of non-manifesting LRRK2 G2019S carriers in the PPMI cohort

Author

Simuni, T, Merchant, K, Brumm, MC, Cho, H, Caspell-Garcia, C, Coffey, CS, Chahine, LM, Alcalay, RN, Nudelman, K, Foroud, T, Mollenhauer, B, Siderowf, A, Tanner, C, Iwaki, H, Sherer, T, Marek, K, Seibyl, J, Coffey, C, Tosun-Turgut, D, Shaw, LM, Trojanowski, JQ, Singleton, A, Kieburtz, K, Toga, A, Galasko, D, Poewe, W, Poston, K, Bressman, S, Reimer, A, Arnedo, V, Clark, A, Frasier, M, Kopil, C, Chowdhury, S, Casaceli, C, Dorsey, R, Wilson, R, Mahes, S, Salerno, C, Ahrens, M, Brumm, M, Cho, HR, Fedler, J, LaFontant, D-E, Kurth, R, Crawford, K, Casalin, P, Malferrari, G, Weisz, MG, Orr-Urtreger, A, Trojanowski, J, Shaw, L, Montine, T, Baglieri, C, Christini, A, Russell, D, Dahodwala, N, Giladi, N, Factor, S, Hogarth, P, Standaert, D, Hauser, R, Jankovic, J, Saint-Hilaire, M, Richard, I, Shprecher, D, Fernandez, H, Brockmann, K, Rosenthal, L, Barone, P, Espayc, A, Rowe, D, Marder, K, Santiago, A, Hu, S-C, Isaacson, S, Corvol, J-C, Martinez, JR, Tolosa, E, Tai, Y, Politis, M, Smejdir, D, Rees, L, Williams, K, Kausar, F, Richardson, W, Willeke, D, Peacock, S, Sommerfeld, B, Freed, A, Wakeman, K, Blair, C, Guthrie, S, Harrell, L, Hunter, C, Thomas, C-A, James, R, Zimmerman, G, Brown, V, Mule, J, Hilt, E, Ribb, K, Ainscough, S, Wethington, M, Ranola, M, Santana, HM, Moreno, J, Raymond, D, Speketer, K, Carvajal, L, Carvalo, S, Croitoru, I, Garrido, A, Payne, LM, Viswanth, V, Severt, L, Facheris, M, Soares, H, Mintun, MA, Cedarbaum, J, Taylor, P, Biglan, K, Vandenbroucke, E, Sheikh, ZH, Bingol, B, Fischer, T, Sardi, P, Forrat, R, Reith, A, Egebjerg, J, Hillert, GA, Saba, B, Min, C, Umek, R, Mather, J, De Santi, S, Post, A, Boess, F, Taylor, K, Grachev, I, Avbersek, A, Muglia, P, Tauscher, J, and Michael J Fox Foundation

Abstract

We examined 2-year longitudinal change in clinical features and biomarkers in LRRK2 non-manifesting carriers (NMCs) versus healthy controls (HCs) enrolled in the Parkinson’s Progression Markers Initiative (PPMI). We analyzed 2-year longitudinal data from 176 LRRK2 G2019S NMCs and 185 HCs. All participants were assessed annually with comprehensive motor and non-motor scales, dopamine transporter (DAT) imaging, and biofluid biomarkers. The latter included cerebrospinal fluid (CSF) Abeta, total tau and phospho-tau; serum urate and neurofilament light chain (NfL); and urine bis(monoacylglycerol) phosphate (BMP). At baseline, LRRK2 G2019S NMCs had a mean (SD) age of 62 (7.7) years and were 56% female. 13% had DAT deficit (defined as

Published
2022

12. Safety and efficacy of anti-tau monoclonal antibody gosuranemab in progressive supranuclear palsy: a phase 2, randomized, placebo-controlled trial (August, 10.1038/s41591-021-01455-x, 2021)

Author

Dam, T, Golbe, LI, Hoglinger, GU, Grundman, M, Yang, LL, Tidemann-Miller, B, Kupferman, J, Harper, K, Kamisoglu, K, Wald, MJ, Graham, DL, Gedney, L, O'Gorman, J, Haeberlein, SB, Aiba, I, Antonini, A, Apetauerova, D, Azulay, JP, Martinez, EB, Bang, J, Barone, P, Barrett, M, Bega, D, Berg, D, Corrales, KB, Bordelon, Y, Boxer, AL, Brandt, M, Brueggemann, N, Castelnovo, G, Ceravolo, R, Chuang, RD, Chung, SJ, Church, A, Corvol, JC, Cudia, P, Dale, M, Defebvre, L, Drapier, S, Driver-Dunckley, ED, Ebersbach, G, Eggert, KM, Ellenbogen, A, Eusebio, A, Evans, AH, Fedorova, N, Finger, E, Foubert-Samier, A, Ghosh, B, Golbe, L, Perez, FG, Grossman, M, Hall, D, Hamada, K, Hasegawa, K, Hoeglinger, G, Honig, L, Houghton, D, Huang, XM, Isaacson, S, Koh, S, Bojarski, JK, Lang, ANE, Leigh, PN, Litvan, I, Lozano, JJL, Moreno, JLLS, Ludolph, AC, Piudo, MRL, Torres, IM, McFarland, N, Meissner, W, Mestre, T, Rivera, PM, Molho, E, Mollenhauer, B, Morris, HR, Murata, M, Obi, T, Magne, FO, O'Suilleabhain, P, Pahwa, R, Pantelyat, A, Pavese, N, Pokhabov, D, Prudlo, J, Rodriguez-Porcel, F, Rowe, J, Savitt, J, Schnitzler, A, Schulz, JB, Seppi, K, Shah, BI, Shill, H, Shprecher, D, Stamelou, M, Steiger, M, Takahashi, Y, Takigawa, H, Tartaglia, C, Toenges, L, Truong, D, Tse, W, Tuite, P, Volc, D, Wills, AMA, Woitalla, D, Xie, T, Yuasa, T, Zauber, SE, and Zesiewicz, T

Published
2022

23. Accurate Particle-Based Reaction Algorithms for Fixed Timestep Simulators

Author

Wood, D, de Gier, J, Praeger, C, Tao, T, Johnston, ST, Angstmann, C, Arjunan, SNV, Beentjes, C, Coulier, A, Isaacson, S, Khan, A, Lipkow, K, Andrews, S, Wood, D, de Gier, J, Praeger, C, Tao, T, Johnston, ST, Angstmann, C, Arjunan, SNV, Beentjes, C, Coulier, A, Isaacson, S, Khan, A, Lipkow, K, and Andrews, S

Abstract

Particle-based simulators are widely used to study biochemical systems involving spatial transport and chemical reactions on sub-cellular length scales. Fixed time step methods can often offer good performance even when simulating complex many-particle systems. However, current reaction algorithms approximate more detailed molecular dynamics models either inaccurately or slowly. Here, we present new reaction algorithms that better approximate microscopic molecular dynamics models while maintaining good computational efficiency. A “Brownian bridge” algorithm samples reactions using reactant positions both before and after each diffusive step; its simulated dynamics exactly match those of appropriate underlying idealised models. Simpler but less accurate “RDF-matching” algorithms sample reactions by only using reactant positions after diffusive steps; they accurately reproduce the steady-state radial distribution function of the underlying idealised model. These algorithms can accurately approximate both commonly used reaction models and more realistic models that account for intermolecular potentials.

Published
2020

30. Efficacy and Safety of AbobotulinumtoxinA (Dysport) for the Treatment of Hemiparesis in Adults With Upper Limb Spasticity Previously Treated With Botulinum Toxin: Subanalysis From a Phase 3 Randomized Controlled Trial

Author

Marciniak, Christina, Mcallister, Peter, Walker, Heather, Brashear, Allison, Edgley, Steven, Deltombe, Thierry, Khatkova, Svetlana, Banach, Marta, Gul, Fatma, Vilain, Claire, Picaut, Philippe, Grandoulier, Anne-Sophie, Gracies, Jean-Michel, Ayyoub, Z., Banach, M., Bensmail, D., Bentivoglio, A. R., Boyer, F. C., Brashear, A., Csanyi, A., Deltombe, T., Denes, Z., Edgley, S., Gul, F., Gracies, J. -M., Hedera, P., Isaacson, S., Isner-Horobeti, M. -E., Jech, R., Kaminska, A., Khatkova, S., Kocer, S., Lejeune, T., Mcallister, P., Marciniak, C., Marque, P., O'Dell, M., Remy-Neris, O., Rubin, B., Rudzinska-Bar, M., Simpson, D., Skoromets, A., Timerbaeva, S. L., Valkovic, P., Vecchio, M., Walker, H., Wimmer, M., UCL - (MGD) Service de médecine physique et revalidation, UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Service de médecine physique et de réadaptation motrice, and UCL - SSS/IREC/NMSK - Neuro-musculo-skeletal Lab

Subjects
Male, 030506 rehabilitation, Physical Therapy, Acetylcholine Release Inhibitors, law.invention, 0302 clinical medicine, Randomized controlled trial, Physical Therapy, Sports Therapy and Rehabilitation, Rehabilitation, Neurology, Neurology (clinical), law, Prospective Studies, Botulinum Toxins, Type A, Aged, 80 and over, education.field_of_study, Middle Aged, Botulinum toxin, Paresis, Settore MED/26 - NEUROLOGIA, Treatment Outcome, medicine.anatomical_structure, Neuromuscular Agents, Muscle Spasticity, Female, medicine.symptom, 0305 other medical science, medicine.drug, Adult, medicine.medical_specialty, Adolescent, Modified Ashworth scale, Population, Sports Therapy and Rehabilitation, Placebo, Injections, Intramuscular, Upper Extremity, Young Adult, 03 medical and health sciences, Muscle tone, Double-Blind Method, medicine, Humans, Spasticity, education, Aged, business.industry, Hemiparesis, Physical therapy, business, 030217 neurology & neurosurgery
Abstract

Objective To assess the efficacy and safety of abobotulinumtoxinA in adults with upper limb spasticity previously treated with botulinum toxin A (BoNT-A). Design A post hoc analysis from a Phase 3, prospective, double-blind, randomized, placebo-controlled study (NCT01313299). Setting A total of 34 neurology or rehabilitation clinics in 9 countries. Participants Adults aged 18-80 years with hemiparesis, ≥6 months after stroke or traumatic brain injury. This analysis focused on a subgroup of subjects with previous onabotulinumtoxinA or incobotulinumtoxinA treatment (n = 105 of 243 in the total trial population) in the affected limb. The mean age was 52 years, and 62% were male. Intervention Study subjects were randomized 1:1:1 to receive a single injection session with abobotulinumtoxinA 500 or 1000 U or with placebo in the most hypertonic muscle group among the elbow, wrist, or finger flexors (primary target muscle group [PTMG]), and ≥2 additional muscle groups from the upper limb. Main Outcome Measurements Efficacy and safety measures were assessed, including muscle tone (Modified Ashworth Scale [MAS] in the PTMG), Physician Global Assessment (PGA), perceived function, spasticity, active movement, and treatment-emergent adverse events. Results At week 4, more subjects had ≥1 grade improvement in MAS for the PTMG with abobotulinumtoxinA versus placebo (abobotulinumtoxinA 500 U, 81.1%; abobotulinumtoxinA 1000 U, 75.0%; placebo, 25.0%). PGA scores ≥1 were achieved by 75.7% and 87.5% of abobotulinumtoxinA 500 and 1000 U subjects versus 41.7% with placebo. Perceived function (Disability Assessment Scale), spasticity angle (Tardieu Scale), and active movement were also improved with abobotulinumtoxinA. There were no treatment-related deaths or serious adverse events. Conclusions The efficacy and safety of abobotulinumtoxinA in subjects previously treated with BoNT-A were consistent with those in the total trial population. Hence, abobotulinumtoxinA is a treatment option in these patients, and no difference in initial dosing appears to be required compared to that in individuals not treated previously. Level of Evidence III

Published
2017

31. Predicting Progression in Parkinson’s Disease Using Baseline and 1-Year Change Measures

Author

Chahine, LM, Siderowf, A, Barnes, J, Seedorff, N, Caspell-Garcia, C, Simuni, T, Coffey, CS, Galasko, D, Mollenhauer, B, Arnedo, V, Daegele, N, Frasier, M, Tanner, C, Kieburtz, K, Marek, K, Seibyl, J, Coffey, C, Tosun-Turgut, D, Shaw, L, Trojanowski, J, Singleton, A, Toga, A, Chahine, L, Poewe, W, Foroud, T, Poston, K, Sherer, T, Chowdhury, S, Kopil, C, Casaceli, C, Dorsey, R, Wilson, R, Mahes, S, Salerno, C, Crawford, K, Casalin, P, Malferrari, G, Weisz, MG, Orr-Urtreger, A, Montine, T, Russell, D, Dahodwala, N, Giladi, N, Factor, S, Hogarth, P, Standaert, D, Hauser, R, Jankovic, J, Saint-Hilaire, M, Richard, I, Shprecher, D, Fernandez, H, Brockmann, K, Rosenthal, L, Barone, P, Espay, A, Rowe, D, Marder, K, Santiago, A, Bressman, S, Hu, S-C, Isaacson, S, Corvol, J-C, Ruiz Martinez, J, Tolosa, E, Tai, Y, Politis, M, Smejdir, D, Rees, L, Williams, K, Kausar, F, Richardson, W, Willeke, D, Peacock, S, Sommerfeld, B, Freed, A, Wakeman, K, Blair, C, Guthrie, S, Harrell, L, Hunter, C, Thomas, C-A, James, R, Zimmerman, G, Brown, V, Mule, J, Hilt, E, Ribb, K, Ainscough, S, Wethington, M, Ranola, M, Santana, HM, Moreno, J, Raymond, D, Speketer, K, Carvajal, L, Carvalho, S, Croitoru, I, Garrido, A, Payne, LM, Viswanth, V, Severt, L, Facheris, M, Soares, H, Mintun, MA, Cedarbaum, J, Taylor, P, Biglan, K, Vandenbroucke, E, Sheikh, ZH, Bingol, B, Fischer, T, Sardi, P, Forrat, R, Reith, A, Egebjerg, J, Hillert, GA, Saba, B, Min, C, Umek, R, Mather, J, De Santi, S, Post, A, Boess, F, Taylor, K, Grachev, I, Avbersek, A, Muglia, P, Merchant, K, Tauscher, J, and Michael J Fox Foundation

Subjects
Male, Research Report, 0301 basic medicine, Movement disorders, Parkinson's disease, MOTOR PROGRESSION, Disease, 0601 Biochemistry and Cell Biology, Severity of Illness Index, Behavior disorder, PROGNOSTIC-FACTORS, 0302 clinical medicine, BOOTSTRAP, Medicine, Parkinson’s disease, biomarkers, disease progression, surrogate endpoint, Prospective Studies, RATING-SCALE, Brain, Parkinson Disease, Middle Aged, SPECT, Female, medicine.symptom, Life Sciences & Biomedicine, medicine.medical_specialty, Disease duration, Rapid eye movement sleep, The Parkinson’s Progression Markers Initiative, 03 medical and health sciences, Cellular and Molecular Neuroscience, Rating scale, Internal medicine, Humans, Aged, Dopamine Plasma Membrane Transport Proteins, Science & Technology, IDENTIFICATION, business.industry, Surrogate endpoint, Neurosciences, medicine.disease, 030104 developmental biology, SLEEP BEHAVIOR DISORDER, Neurosciences & Neurology, Neurology (clinical), sense organs, TAU, 1109 Neurosciences, business, 030217 neurology & neurosurgery
Abstract

Author(s): Chahine, Lana M; Siderowf, Andrew; Barnes, Janel; Seedorff, Nicholas; Caspell-Garcia, Chelsea; Simuni, Tanya; Coffey, Christopher S; Galasko, Douglas; Mollenhauer, Brit; Arnedo, Vanessa; Daegele, Nichole; Frasier, Mark; Tanner, Caroline; Kieburtz, Karl; Marek, Kenneth; The Parkinson’s Progression Markers Initiative | Abstract: BackgroundImproved prediction of Parkinson's disease (PD) progression is needed to support clinical decision-making and to accelerate research trials.ObjectivesTo examine whether baseline measures and their 1-year change predict longer-term progression in early PD.MethodsParkinson's Progression Markers Initiative study data were used. Participants had disease duration ≤2 years, abnormal dopamine transporter (DAT) imaging, and were untreated with PD medications. Baseline and 1-year change in clinical, cerebrospinal fluid (CSF), and imaging measures were evaluated as candidate predictors of longer-term (up to 5 years) change in Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) score and DAT specific binding ratios (SBR) using linear mixed-effects models.ResultsAmong 413 PD participants, median follow-up was 5 years. Change in MDS-UPDRS from year-2 to last follow-up was associated with disease duration (β= 0.351; 95% CI = 0.146, 0.555), male gender (β= 3.090; 95% CI = 0.310, 5.869), and baseline (β= -0.199; 95% CI = -0.315, -0.082) and 1-year change (β= 0.540; 95% CI = 0.423, 0.658) in MDS-UPDRS; predictors in the model accounted for 17.6% of the variance in outcome. Predictors of percent change in mean SBR from year-2 to last follow-up included baseline rapid eye movement sleep behavior disorder score (β= -0.6229; 95% CI = -1.2910, 0.0452), baseline (β= 7.232; 95% CI = 2.268, 12.195) and 1-year change (β= 45.918; 95% CI = 35.994,55.843) in mean striatum SBR, and 1-year change in autonomic symptom score (β= -0.325;95% CI = -0.695, 0.045); predictors in the model accounted for 44.1% of the variance.ConclusionsBaseline clinical, CSF, and imaging measures in early PD predicted change in MDS-UPDRS and dopamine-transporter binding, but the predictive value of the models was low. Adding the short-term change of possible predictors improved the predictive value, especially for modeling change in dopamine-transporter binding.

Published
2019

34. A Double-Blind, Delayed-Start Trial of Rasagiline in Parkinson's Disease

Author

Olanow, Cw, Rascol, O, Hauser, R, Feigin, Pd, Jankovic, J, Lang, A, Langston, W, Melamed, E, Poewe, W, Stocchi, F, Tolosa, E, ADAGIO STUDY INVESTIGATORS, Collaborators, Bueri, J, Garretto, N, Gershanik, O, Giannaula, R, Micheli, F, Wolf, E, Guttman, M, Hobson, D, Jog, M, King, D, Mendis, T, Miyasaki, J, Panisset, M, Pourcher, E, Rajput, A, Ranawaya, R, Tsui, J, Cesaro, P, Damier, P, Destee, A, Durif, F, Slaoui, T, Tison, F, Viallet, F, Deuschl, G, Gasser, T, Ludolph, A, Oehlwein, C, Przuntek, H, Reifschneider, G, Schnitzler, A, Trenkwalder, C, Bokor, M, Katona, A, Lajtos, J, Nikl, J, Takats, A, Valikovics, A, Badarny, S, Djaldetti, R, Giladi, N, Hassin, S, Rabey, Jm, Reches, A, Schwartz, M, Wirguin, I, Albanese, A, Bentivoglio, A, Bonuccelli, U, Calzetti, S, Comi, G, Curatola, L, Ferrarese, C, Lamberti, P, Marconi, R, Martignoni, E, Meco, Giuseppe, Ruggieri, Stefano, Bomhof, Ma, Hovestadt, A, Krul, Jm, Leenders, Kl, Cunha, L, Ferreira, J, Bajenaru, Oa, Carciumaru, N, Bulboaca, Ac, Pascu, I, Simu, M, Calopa, M, FERNÁNDEZ GARCÍA JM, Kulisevsky, J, Linazasoro, C, Miquel, F, Posada, Ij, Martí, Mj, Burn, D, Macmahon, D, Barker, R, Allen, N, Barbour, P, Bertoni, J, Bharucha, K, Bose, S, Drasby, E, Elble, R, Elmer, L, Evans, B, Factor, S, Fernandez, H, Friedman, J, Hull, K, Golbe, L, Goudreau, J, Guttuso, T, Hassan, M, Hermanowicz, N, Houser, M, Hurtig, H, Isaacson, S, Jennings, D, Kompoliti, A, Morgan, J, Murphy, J, Nausieda, P, Pahwa, R, Parashos, S, O'Suilleabhain, P, Racette, B, Reich, S, Roberts, J, Rothstein, T, Sahay, A, SAINT HILAIRE, M, Schiess, M, Scott, B, Shahed, J, Simuni, T, Singer, C, Smith, R, Struck, L, Sutton, J, Swope, D, Tagliati, M, Tetrud, J, Togasaki, D, Watts, R., Olanow, C, Rascol, O, Hauser, R, Feigin, P, Jankovic, J, Lang, A, Langston, W, Melamed, E, Poewe, W, Stocchi, F, Tolosa, E, ADAGIO Study, I, Bueri, J, Garretto, N, Gershanik, O, Giannaula, R, Micheli, F, Wolf, E, Guttman, M, Hobson, D, Jog, M, King, D, Mendis, T, Miyasaki, J, Panisset, M, Pourcher, E, Rajput, A, Ranawaya, R, Tsui, J, Cesaro, P, Damier, P, Destee, A, Durif, F, Slaoui, T, Tison, F, Viallet, F, Deuschl, G, Gasser, T, Ludolph, A, Oehlwein, C, Przuntek, H, Reifschneider, G, Schnitzler, A, Trenkwalder, C, Bokor, M, Katona, A, Lajtos, J, Nikl, J, Takats, A, Valikovics, A, Badarny, S, Djaldetti, R, Giladi, N, Hassin, S, Rabey, J, Reches, A, Schwartz, M, Wirguin, I, Albanese, A, Bentivoglio, A, Bonuccelli, U, Calzetti, S, Comi, G, Curatola, L, Ferrarese, C, Lamberti, P, Marconi, R, Martignoni, E, Meco, G, Ruggieri, S, Bomhof, M, Hovestadt, A, Krul, J, Leenders, K, Cunha, L, Ferreira, J, Bajenaru, O, Carciumaru, N, Bulboaca, A, Pascu, I, Simu, M, Calopa, M, Fernández García, J, Kulisevsky, J, Linazasoro, C, Miquel, F, Posada, I, Martí, M, Burn, D, Macmahon, D, Barker, R, Allen, N, Barbour, P, Bertoni, J, Bharucha, K, Bose, S, Drasby, E, Elble, R, Elmer, L, Evans, B, Factor, S, Fernandez, H, Friedman, J, Hull, K, Golbe, L, Goudreau, J, Guttuso, T, Hassan, M, Hermanowicz, N, Houser, M, Hurtig, H, Isaacson, S, Jennings, D, Kompoliti, A, Morgan, J, Murphy, J, Nausieda, P, Pahwa, R, Parashos, S, O'Suilleabhain, P, Racette, B, Reich, S, Roberts, J, Rothstein, T, Sahay, A, Saint Hilaire, M, Schiess, M, Scott, B, Shahed, J, Simuni, T, Singer, C, Smith, R, Struck, L, Sutton, J, Swope, D, Tagliati, M, Tetrud, J, Togasaki, D, and Watts, R

Subjects
Adult, Male, medicine.medical_specialty, Monoamine Oxidase Inhibitors, Parkinson's disease, Neuroprotective Agent, Severe disease, Placebo, Severity of Illness Index, Placebo group, Drug Administration Schedule, Central nervous system disease, Double blind, chemistry.chemical_compound, Double-Blind Method, Severity of illness, Humans, Rasagiline, Medicine, Monoamine Oxidase Inhibitor, Aged, Dose-Response Relationship, Drug, business.industry, Indan, Parkinson Disease, General Medicine, Middle Aged, medicine.disease, Surgery, Neuroprotective Agents, chemistry, Research Design, Anesthesia, Indans, Female, business, Human
Abstract

BACKGROUND: A therapy that slows disease progression is the major unmet need in Parkinson's disease. METHODS: In this double-blind trial, we examined the possibility that rasagiline has disease-modifying effects in Parkinson's disease. A total of 1176 subjects with untreated Parkinson's disease were randomly assigned to receive rasagiline (at a dose of either 1 mg or 2 mg per day) for 72 weeks (the early-start group) or placebo for 36 weeks followed by rasagiline (at a dose of either 1 mg or 2 mg per day) for 36 weeks (the delayed-start group). To determine a positive result with either dose, the early-start treatment group had to meet each of three hierarchical end points of the primary analysis based on the Unified Parkinson's Disease Rating Scale (UPDRS, a 176-point scale, with higher numbers indicating more severe disease): superiority to placebo in the rate of change in the UPDRS score between weeks 12 and 36, superiority to delayed-start treatment in the change in the score between baseline and week 72, and noninferiority to delayed-start treatment in the rate of change in the score between weeks 48 and 72. RESULTS: Early-start treatment with rasagiline at a dose of 1 mg per day met all end points in the primary analysis: a smaller mean (+/-SE) increase (rate of worsening) in the UPDRS score between weeks 12 and 36 (0.09+/-0.02 points per week in the early-start group vs. 0.14+/-0.01 points per week in the placebo group, P=0.01), less worsening in the score between baseline and week 72 (2.82+/-0.53 points in the early-start group vs. 4.52+/-0.56 points in the delayed-start group, P=0.02), and noninferiority between the two groups with respect to the rate of change in the UPDRS score between weeks 48 and 72 (0.085+/-0.02 points per week in the early-start group vs. 0.085+/-0.02 points per week in the delayed-start group, P

Published
2009

40. Clinical correlates of longitudinal brain atrophy in progressive supranuclear palsy

Author

Tsai, RM, Lobach, I, Bang, J, Whitwell, JL, Senjem, ML, Jack, CR, Rosen, H, Miller, B, Boxer, AL, Williams, D, Lafontaine, AL, Marras, C, Jog, M, Panisset, M, Lang, A, Parker, L, Stewart, AJ, Corvol, JC, Azulay, JP, Couratier, P, Mollenhauer, B, Lorenzl, S, Ludolph, A, Benecke, R, Hoglinger, G, Lipp, A, Reichmann, H, Woitalla, D, Chan, D, Zermansky, A, Burn, D, Lees, A, Gozes, I, Boxer, A, Miller, BL, Lobach, IV, Roberson, ED, Honig, L, Zamrini, E, Pahwa, R, Bordelon, Y, Driver-Dunkley, E, Lessig, S, Lew, M, Womack, K, Boeve, B, Ferrara, J, Hillis, A, Kaufer, D, Kumar, R, Xie, T, Gunzler, S, Zesiewicz, T, Dayalu, P, Golbe, L, Jankovic, J, McGinnis, S, Santiago, A, Tuite, P, Isaacson, S, Leegwater-Kim, J, Litvan, I, Grossman, M, Knopman, DS, Schneider, LS, Doody, RS, Golbe, LI, Koestler, M, Deerlin, VV, Randolph, C, Whitaker, S, Hirman, J, Gold, M, and Morimoto, BH

Subjects
Clinical trials, Progressive supranuclear palsy, Biomarkers, Imaging, MRI
Abstract

© 2016 . Introduction: There are no effective treatments for progressive supranuclear palsy (PSP). Volumetric MRI (vMRI) may be a useful surrogate outcome measure in PSP clinical trials. The goal of the study was to evaluate the potential of vMRI to correlate with clinical outcomes from an international clinical trial population. Methods: PSP patients (n = 198) from the AL-108-231 trial who had high quality vMRI and Progressive Supranuclear Palsy Rating Scale (PSPRS), Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Schwab and England Activities of Daily Living (SEADL), Color Trails Test, Geriatric Depression Screen (GDS) and one year Clinician Global Impression of Change (CGIC) data from the baseline and 52 week visits were included. Linear regression was used to relate baseline values and annual clinical rating scale changes to annual regional vMRI changes (whole brain, ventricular, midbrain and superior cerebellar peduncle volumes). Results: Effect sizes (Cohen's d) measuring disease progression over one year were largest for vMRI (midbrain [1.27] and ventricular volume [1.31]) but similar to PSPRS (1.26). After multiple comparison adjustment, annual changes in PSPRS, RBANS, SEADL, Color Trails Test, GDS and one year CGIC were modestly correlated with annual vMRI changes (p < 0.05). Baseline neuropsychological status on RBANS (p = 0.019) and Color Trails (p < 0.01) predicted annual midbrain atrophy rates. Conclusion: Standard vMRI measurements are sensitive to disease progression in large, multicenter PSP clinical trials, but are not well correlated with clinical changes. vMRI changes may be useful as supportive endpoints in PSP trials.

Published
2016

41. Power calculations and placebo effect for future clinical trials in progressive supranuclear palsy

Author

Stamelou, M, Schöpe, J, Wagenpfeil, S, Del Ser, T, Bang, J, Lobach, IY, Luong, P, Respondek, G, Oertel, WH, Boxer, A, Höglinger, GU, Williams, D, Lafontaine, AL, Marras, C, Jog, M, Panisset, M, Lang, A, Parker, L, Stewart, AJ, Corvol, JC, Azulay, JP, Couratier, P, Mollenhauer, B, Lorenzl, S, Ludolph, A, Benecke, R, Hoglinger, G, Lipp, A, Reichmann, H, Woitalla, D, Chan, D, Zermansky, A, Burn, D, Lees, A, Miller, BL, Lobach, IV, Roberson, E, Honig, L, Zamrini, E, Pahwa, R, Bordelon, Y, Driver-Dunkley, E, Lessig, S, Lew, M, Womack, K, Boeve, B, Ferrara, J, Hillis, A, Kaufer, D, Kumar, R, Xie, T, Gunzler, S, Zesiewicz, T, Dayalu, P, Golbe, L, Grossman, M, Jankovic, J, McGinnis, S, Santiago, A, Tuite, P, Isaacson, S, Leegwater-Kim, J, Litvan, I, Knopman, DS, Schneider, LS, Doody, RS, Koestler, M, Jack, CR, Van Deerlin, V, Randolph, C, Gozes, I, Whitaker, S, Hirman, J, Gold, M, Morimoto, BH, Gómez, JC, Tijero, B, Berganzo, K, García de Yebenes, J, Lopez Sendón, JL, Garcia, G, Tolosa, E, Buongiorno, MT, Bargalló, N, Burguera, JA, Martinez, I, Ruiz-Martínez, J, and Narrativel, I

Subjects
eye diseases
Abstract

© 2016 International Parkinson and Movement Disorder Society. Background: Two recent randomized, placebo-controlled trials of putative disease-modifying agents (davunetide, tideglusib) in progressive supranuclear palsy (PSP) failed to show efficacy, but generated data relevant for future trials. Methods: We provide sample size calculations based on data collected in 187 PSP patients assigned to placebo in these trials. A placebo effect was calculated. Results: The total PSP-Rating Scale required the least number of patients per group (N=51) to detect a 50% change in the 1-year progression and 39 when including patients with ≤ 5 years disease duration. The Schwab and England Activities of Daily Living required 70 patients per group and was highly correlated with the PSP-Rating Scale. A placebo effect was not detected in these scales. Conclusions: We propose the 1-year PSP-Rating Scale score change as the single primary readout in clinical neuroprotective or disease-modifying trials. The Schwab and England Activities of Daily Living could be used as a secondary outcome.

Published
2016

42. Power calculations and placebo effect for future clinical trials in progressive supranuclear palsy

Author

Stamelou, M. Schöpe, J. Wagenpfeil, S. Del Ser, T. Bang, J. Lobach, I.Y. Luong, P. Respondek, G. Oertel, W.H. Boxer, A. Höglinger, G.U. Williams, D. Lafontaine, A.L. Marras, C. Jog, M. Panisset, M. Lang, A. Parker, L. Stewart, A.J. Corvol, J.-C. Azulay, J.-P. Couratier, P. Mollenhauer, B. Lorenzl, S. Ludolph, A. Benecke, R. Hoglinger, G. Lipp, A. Reichmann, H. Woitalla, D. Chan, D. Zermansky, A. Burn, D.J. Lees, A. Boxer, A. Miller, B.L. Lobach, I.V. Roberson, E. Honig, L. Zamrini, E. Pahwa, R. Bordelon, Y. Driver-Dunkley, E. Lessig, S. Lew, M. Womack, K. Boeve, B. Ferrara, J. Hillis, A. Kaufer, D. Kumar, R. Xie, T. Gunzler, S. Zesiewicz, T. Dayalu, P. Golbe, L. Grossman, M. Jankovic, J. McGinnis, S. Santiago, A. Tuite, P. Isaacson, S. Leegwater-Kim, J. Litvan, I. Grossman, M. Knopman, D.S. Schneider, L.S. Doody, R.S. Golbe, L. Koestler, M. Jack, C.R. Van Deerlin, V. Randolph, C. Gozes, I. Whitaker, S. Hirman, J. Gold, M. Morimoto, B.H. Gómez, J.C. Tijero, B. Berganzo, K. García de Yebenes, J. Lopez Sendón, J.L. Garcia, G. Tolosa, E. Buongiorno, M.T. Bargalló, N. Burguera, J.A. Martinez, I. Ruiz-Martínez, J. Narrativel, I. Vivancos, F. Ybot, I. Aguilar, M. Quilez, P. Boada, M. Lafuente, A. Hernandez, I. López-Lozano, J.J. Mata, M. Kupsch, A. Lipp, A. Ebersbach, G. Schmidt, T. Hahn, K. Hoglinger, G. Hollerhage, M. Reichmann, H. Wolz, M. Schneider, C. Klingelhofer, L. Berg, D. Maetzler, W. Srulijes, K.K. Ludolph, A. Kassubek, J. Steiger, M. Tyler, K. Morris, L. Lees, A. Ling, H. Hauser, R. McClain, T. Truong, D. Jenkins, S. Litvan, I. Houghton, D. Ferrara, J. Bordelon, Y. Gratiano, A. Golbe, L. Mark, M. Uitti, R. Ven Gerpen, J. Bhatia, K. Bordelon, Y.M. Colosimo, C. Dodel, R. Josephs, K.A. Morris, H. Mueller, U. Paviour, D. Schellenberg, G. Steele, J. van Swieten, J.C. Whitwell, J. Tau Restoration on PSP (TAUROS) Investigators The MDS-Endorsed PSP Study Group

Subjects
eye diseases
Abstract

Background: Two recent randomized, placebo-controlled trials of putative disease-modifying agents (davunetide, tideglusib) in progressive supranuclear palsy (PSP) failed to show efficacy, but generated data relevant for future trials. Methods: We provide sample size calculations based on data collected in 187 PSP patients assigned to placebo in these trials. A placebo effect was calculated. Results: The total PSP-Rating Scale required the least number of patients per group (N=51) to detect a 50% change in the 1-year progression and 39 when including patients with ≤ 5 years disease duration. The Schwab and England Activities of Daily Living required 70 patients per group and was highly correlated with the PSP-Rating Scale. A placebo effect was not detected in these scales. Conclusions: We propose the 1-year PSP-Rating Scale score change as the single primary readout in clinical neuroprotective or disease-modifying trials. The Schwab and England Activities of Daily Living could be used as a secondary outcome. © 2016 International Parkinson and Movement Disorder Society.

Published
2016

47. Safety and efficacy of abobotulinumtoxinA for hemiparesis in adults with upper limb spasticity after stroke or traumatic brain injury : a double-blind randomised controlled trial

Author

Gracies, J, Brashear, A, Jech, R, Mcallister, P, Banach, M, Valkovic, P, Walker, H, Marciniak, C, Deltombe, T, Skoromets, A, Khatkova, S, Edgley, S, Gul, F, Catus, F, De Fer, Bb, Vilain, C, Picaut, P, Ayyoub, Z, Bensmail, D, Bentivoglio, Anna Rita, Boyer, F, Csanyi, A, Denes, Z, Gracies, Jm, Hedera, P, Isaacson, S, Isner Horobeti, Me, Kaminska, A, Kocer, S, Lejeune, T, Marque, P, O'Dell, M, Remy Neris, O, Rubin, B, Rudzinska, M, Simpson, D, Timerbaeva, Sl, Vecchio, M, and Wimmer, M.

Subjects
Adult, Male, medicine.medical_specialty, Botulinum Toxins, Modified Ashworth scale, Acetylcholine Release Inhibitors, Placebo, Injections, Intramuscular, law.invention, Type A, Injections, Upper Extremity, Muscle tone, Randomized controlled trial, Double-Blind Method, law, Spastic, medicine, Humans, Spasticity, Botulinum Toxins, Type A, Intramuscular, Intention-to-treat analysis, business.industry, Middle Aged, Paresis, Stroke, Settore MED/26 - NEUROLOGIA, medicine.anatomical_structure, Hemiparesis, Treatment Outcome, Muscle Spasticity, Anesthesia, Brain Injuries, Physical therapy, Female, Neurology (clinical), medicine.symptom, business
Abstract

Summary Background Resistance from antagonistic muscle groups might be a crucial factor reducing function in chronic hemiparesis. The resistance due to spastic co-contraction might be reduced by botulinum toxin injections. We assessed the effects of abobotulinumtoxinA injection in the upper limb muscles on muscle tone, spasticity, active movement, and function. Methods In this randomised, placebo-controlled, double-blind study, we enrolled adults (aged 18–80 years) at least 6 months after stroke or brain trauma from 34 neurology or rehabilitation clinics in Europe and the USA. Eligible participants were randomly allocated in a 1:1:1 ratio with a computer-generated list to receive a single injection session of abobotulinumtoxinA 500 U or 1000 U or placebo into the most hypertonic muscle group among the elbow, wrist, or finger flexors (primary target muscle group [PTMG]), and into at least two additional muscle groups from the elbow, wrist, or finger flexors or shoulder extensors. Patients and investigators were masked to treatment allocation. The primary endpoint was the change in muscle tone (Modified Ashworth Scale [MAS]) in the PTMG from baseline to 4 weeks. Secondary endpoints were Physician Global Assessment (PGA) at week 4 and change from baseline to 4 weeks in the perceived function (Disability Assessment Scale [DAS]) in the principal target of treatment, selected by the patient together with physician from four functional domains (dressing, hygiene, limb position, and pain). Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01313299. Findings 243 patients were randomly allocated to placebo (n=81), abobotulinumtoxinA 500 U (n=81), or abobotulinumtoxinA 1000 U (n=81). Mean change in MAS score from baseline at week 4 in the PTMG was −0·3 (SD 0·6) in the placebo group (n=79), −1·2 (1·0) in the abobotulinumtoxinA 500 U group (n=80; difference −0·9, 95% CI −1·2 to −0·6; p vs placebo), and −1·4 (1·1) in the abobotulinumtoxinA 1000 U group (n=79; −1·1, −1·4 to −0·8; p vs placebo). Mean PGA score at week 4 was 0·6 (SD 1·0) in the placebo group (n=78), 1·4 (1·1) in the abobotulinumtoxinA 500 U group (n=80; p=0·0003 vs placebo), and 1·8 (1·1) in the abobotulinumtoxinA 1000 U group (n=78; p vs placebo). Mean change from baseline at week 4 in DAS score for the principal target of treatment was −0·5 (0·7) in the placebo group (n=79), −0·7 (0·8) in the abobotulinumtoxinA 500 U group (n=80; p=0·2560 vs placebo), and −0·7 (0·7) in the abobotulinumtoxinA 1000 U group (n=78; p=0·0772 vs placebo). Three serious adverse events occurred in each group and none were treatment related; two resulted in death (from pulmonary oedema in the placebo group and a pre-existing unspecified cardiovascular disorder in the abobotulinumtoxinA 500 U group). Adverse events that were thought to be treatment related occurred in two (2%), six (7%), and seven (9%) patients in the placebo, abobotulinumtoxinA 500 U, and abobotulinumtoxinA 1000 U groups, respectively. The most common treatment-related adverse event was mild muscle weakness. All adverse events were mild or moderate. Interpretation AbobotulinumtoxinA at doses of 500 U or 1000 U injected into upper limb muscles provided tone reduction and clinical benefit in hemiparesis. Future research into the treatment of spastic paresis with botulinum toxin should use active movement and function as primary outcome measures. Funding Ipsen.

Published
2015

48. Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease

Author

Nalls, M.A. Pankratz, N. Lill, C.M. Do, C.B. Hernandez, D.G. Saad, M. Destefano, A.L. Kara, E. Bras, J. Sharma, M. Schulte, C. Keller, M.F. Arepalli, S. Letson, C. Edsall, C. Stefansson, H. Liu, X. Pliner, H. Lee, J.H. Cheng, R. Ikram, M.A. Ioannidis, J.P.A. Hadjigeorgiou, G.M. Bis, J.C. Martinez, M. Perlmutter, J.S. Goate, A. Marder, K. Fiske, B. Sutherland, M. Xiromerisiou, G. Myers, R.H. Clark, L.N. Stefansson, K. Hardy, J.A. Heutink, P. Chen, H. Wood, N.W. Houlden, H. Payami, H. Brice, A. Scott, W.K. Gasser, T. Bertram, L. Eriksson, N. Foroud, T. Singleton, A.B. Plagnol, V. Sheerin, U.-M. Simón-Sánchez, J. Lesage, S. Sveinbjörnsdóttir, S. Barker, R. Ben-Shlomo, Y. Berendse, H.W. Berg, D. Bhatia, K. de Bie, R.M.A. Biffi, A. Bloem, B. Bochdanovits, Z. Bonin, M. Bras, J.M. Brockmann, K. Brooks, J. Burn, D.J. Charlesworth, G. Chinnery, P.F. Chong, S. Clarke, C.E. Cookson, M.R. Cooper, J.M. Corvol, J.C. Counsell, C. Damier, P. Dartigues, J.-F. Deloukas, P. Deuschl, G. Dexter, D.T. van Dijk, K.D. Dillman, A. Durif, F. Dürr, A. Edkins, S. Evans, J.R. Foltynie, T. Dong, J. Gardner, M. Gibbs, J.R. Gray, E. Guerreiro, R. Harris, C. van Hilten, J.J. Hofman, A. Hollenbeck, A. Holton, J. Hu, M. Huang, X. Wurster, I. Mätzler, W. Hudson, G. Hunt, S.E. Huttenlocher, J. Illig, T. Jónsson, P.V. Lambert, J.-C. Langford, C. Lees, A. Lichtner, P. Limousin, P. Lopez, G. Lorenz, D. McNeill, A. Moorby, C. Moore, M. Morris, H.R. Morrison, K.E. Mudanohwo, E. O’sullivan, S.S. Pearson, J. Pétursson, H. Pollak, P. Post, B. Potter, S. Ravina, B. Revesz, T. Riess, O. Rivadeneira, F. Rizzu, P. Ryten, M. Sawcer, S. Schapira, A. Scheffer, H. Shaw, K. Shoulson, I. Sidransky, E. Smith, C. Spencer, C.C.A. Stefánsson, H. Bettella, F. Stockton, J.D. Strange, A. Talbot, K. Tanner, C.M. Tashakkori-Ghanbaria, A. Tison, F. Trabzuni, D. Traynor, B.J. Uitterlinden, A.G. Velseboer, D. Vidailhet, M. Walker, R. van de Warrenburg, B. Wickremaratchi, M. Williams, N. Williams-Gray, C.H. Winder-Rhodes, S. Stefánsson, K. Hardy, J. Factor, S. Higgins, D. Evans, S. Shill, H. Stacy, M. Danielson, J. Marlor, L. Williamson, K. Jankovic, J. Hunter, C. Simon, D. Ryan, P. Scollins, L. Saunders-Pullman, R. Boyar, K. Costan-Toth, C. Ohmann, E. Sudarsky, L. Joubert, C. Friedman, J. Chou, K. Fernandez, H. Lannon, M. Galvez-Jimenez, N. Podichetty, A. Thompson, K. Lewitt, P. Deangelis, M. O'brien, C. Seeberger, L. Dingmann, C. Judd, D. Marder, K. Fraser, J. Harris, J. Bertoni, J. Peterson, C. Rezak, M. Medalle, G. Chouinard, S. Panisset, M. Hall, J. Poiffaut, H. Calabrese, V. Roberge, P. Wojcieszek, J. Belden, J. Jennings, D. Marek, K. Mendick, S. Reich, S. Dunlop, B. Jog, M. Horn, C. Uitti, R. Turk, M. Ajax, T. Mannetter, J. Sethi, K. Carpenter, J. Dill, B. Hatch, L. Ligon, K. Narayan, S. Blindauer, K. Abou-Samra, K. Petit, J. Elmer, L. Aiken, E. Davis, K. Schell, C. Wilson, S. Velickovic, M. Koller, W. Phipps, S. Feigin, A. Gordon, M. Hamann, J. Licari, E. Marotta-Kollarus, M. Shannon, B. Winnick, R. Simuni, T. Videnovic, A. Kaczmarek, A. Williams, K. Wolff, M. Rao, J. Cook, M. Fernandez, M. Kostyk, S. Hubble, J. Campbell, A. Reider, C. Seward, A. Camicioli, R. Carter, J. Nutt, J. Andrews, P. Morehouse, S. Stone, C. Mendis, T. Grimes, D. Alcorn-Costa, C. Gray, P. Haas, K. Vendette, J. Sutton, J. Hutchinson, B. Young, J. Rajput, A. Klassen, L. Shirley, T. Manyam, B. Simpson, P. Whetteckey, J. Wulbrecht, B. Truong, D. Pathak, M. Frei, K. Luong, N. Tra, T. Tran, A. Vo, J. Lang, A. Kleiner-Fisman, G. Nieves, A. Johnston, L. So, J. Podskalny, G. Giffin, L. Atchison, P. Allen, C. Martin, W. Wieler, M. Suchowersky, O. Furtado, S. Klimek, M. Hermanowicz, N. Niswonger, S. Shults, C. Fontaine, D. Aminoff, M. Christine, C. Diminno, M. Hevezi, J. Dalvi, A. Kang, U. Richman, J. Uy, S. Sahay, A. Gartner, M. Schwieterman, D. Hall, D. Leehey, M. Culver, S. Derian, T. Demarcaida, T. Thurlow, S. Rodnitzky, R. Dobson, J. Lyons, K. Pahwa, R. Gales, T. Thomas, S. Shulman, L. Weiner, W. Dustin, K. Singer, C. Zelaya, L. Tuite, P. Hagen, V. Rolandelli, S. Schacherer, R. Kosowicz, J. Gordon, P. Werner, J. Serrano, C. Roque, S. Kurlan, R. Berry, D. Gardiner, I. Hauser, R. Sanchez-Ramos, J. Zesiewicz, T. Delgado, H. Price, K. Rodriguez, P. Wolfrath, S. Pfeiffer, R. Davis, L. Pfeiffer, B. Dewey, R. Hayward, B. Johnson, A. Meacham, M. Estes, B. Walker, F. Hunt, V. O'neill, C. Racette, B. Swisher, L. Dijamco, C. Conley, E.D. Dorfman, E. Tung, J.Y. Hinds, D.A. Mountain, J.L. Wojcicki, A. Lew, M. Klein, C. Golbe, L. Growdon, J. Wooten, G.F. Watts, R. Guttman, M. Goldwurm, S. Saint-Hilaire, M.H. Baker, K. Litvan, I. Nicholson, G. Nance, M. Drasby, E. Isaacson, S. Burn, D. Pramstaller, P. Al-Hinti, J. Moller, A. Sherman, S. Roxburgh, R. Slevin, J. Perlmutter, J. Mark, M.H. Huggins, N. Pezzoli, G. Massood, T. Itin, I. Corbett, A. Chinnery, P. Ostergaard, K. Snow, B. Cambi, F. Kay, D. Samii, A. Agarwal, P. Roberts, J.W. Higgins, D.S. Molho, E. Rosen, A. Montimurro, J. Martinez, E. Griffith, A. Kusel, V. Yearout, D. Factor, S. Zabetian, C. Clark, L.N. Liu, X. Lee, J.H. Cheng Taub, R. Louis, E.D. Cote, L.J. Waters, C. Ford, B. Fahn, S. Vance, J.M. Beecham, G.W. Martin, E.R. Nuytemans, K. Pericak-Vance, M.A. Haines, J.L. Destefano, A. Seshadri, S. Choi, S.H. Frank, S. Bis, J.C. Psaty, B.M. Rice, K. Longstreth, W.T., Jr. Ton, T.G.N. Jain, S. van Duijn, C.M. Uitterlinden, A.G. Verlinden, V.J. Koudstaal, P.J. Singleton, A. Cookson, M. Gibbs, J.R. Hernandez, D. Nalls, M. Zonderman, A. Ferrucci, L. Johnson, R. Longo, D. O'brien, R. Traynor, B. Troncoso, J. van der Brug, M. Zielke, R. Weale, M. Ramasamy, A. Dardiotis, E. Tsimourtou, V. Spanaki, C. Plaitakis, A. Bozi, M. Stefanis, L. Vassilatis, D. Koutsis, G. Panas, M. Hadjigeorgiou, G.M. Lunnon, K. Lupton, M. Powell, J. Parkkinen, L. Ansorge, O. International Parkinson's Disease Genomics Consortium (IPDGC) Parkinson's Study Group (PSG) Parkinson's Research: The Organized GENetics Initiative (PROGENI) 23andMe GenePD NeuroGenetics Research Consortium (NGRC) Hussman Institute of Human Genomics (HIHG) The Ashkenazi Jewish Dataset Investigator Cohorts for Health Aging Research in Genetic Epidemiology (CHARGE) North American Brain Expression Consortium (NABEC) United Kingdom Brain Expression Consortium (UKBEC) Greek Parkinson's Disease Consortium Alzheimer Genetic Analysis Group

Abstract

We conducted a meta-analysis of Parkinson's disease genome-wide association studies using a common set of 7,893,274 variants across 13,708 cases and 95,282 controls. Twenty-six loci were identified as having genome-wide significant association; these and 6 additional previously reported loci were then tested in an independent set of 5,353 cases and 5,551 controls. Of the 32 tested SNPs, 24 replicated, including 6 newly identified loci. Conditional analyses within loci showed that four loci, including GBA, GAK-DGKQ, SNCA and the HLA region, contain a secondary independent risk variant. In total, we identified and replicated 28 independent risk variants for Parkinson's disease across 24 loci. Although the effect of each individual locus was small, risk profile analysis showed substantial cumulative risk in a comparison of the highest and lowest quintiles of genetic risk (odds ratio (OR) = 3.31, 95% confidence interval (CI) = 2.55-4.30; P = 2 × 10-16). We also show six risk loci associated with proximal gene expression or DNA methylation. © 2014 Nature America, Inc. All rights reserved.

Published
2014

Catalog

Books, media, physical & digital resources
See catalog results