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219 results on '"Tennekoon, G."'

1. Characterization of pulmonary function in 10–18 year old patients with Duchenne muscular dystrophy

Author

Bernert, G., Knipp, F., Buyse, G.M., Goemans, N., Van den Hauwe, M., Voit, T., Doppler, V., Gidaro, T., Cuisset, J.-M., Coopman, S., Schara, U., Lutz, S., Kirschner, J., Borell, S., Will, M., D'Angelo, M.G., Brighina, E., Gandossini, S., Gorni, K., Falcier, E., Politano, L., D'Ambrosio, P., Taglia, A., Verschuuren, J.J.G.M., Straathof, C.S.M., Vílchez Padilla, J.J., Muelas Gómez, N., Sejersen, T., Hovmöller, M., Jeannet, P.-Y., Bloetzer, C., Iannaccone, S., Castro, D., Tennekoon, G., Finkel, R., Bönnemann, C., McDonald, C., Henricson, E., Joyce, N., Apkon, S., Richardson, R.C., Meier, Thomas, Rummey, Christian, Leinonen, Mika, Spagnolo, Paolo, Mayer, Oscar H., and Buyse, Gunnar M.

Published
2017
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2. Idebenone reduces respiratory complications in patients with Duchenne muscular dystrophy

Author

Bernert, G., Knipp, F., Buyse, G.M., Goemans, N., van den Hauwe, M., Voit, T., Doppler, V., Gidaro, T., Cuisset, J.-M., Coopman, S., Schara, U., Lutz, S., Kirschner, J., Borell, S., Will, M., D'Angelo, M.G., Brighina, E., Gandossini, S., Gorni, K., Falcier, E., Politano, L., D'Ambrosio, P., Taglia, A., Verschuuren, J.J.G.M., Straathof, C.S.M., Vílchez Padilla, J.J., Muelas Gómez, N., Sejersen, T., Hovmöller, M., Jeannet, P.-Y., Bloetzer, C., Iannaccone, S., Castro, D., Tennekoon, G., Finkel, R., Bönnemann, C., McDonald, C., Henricson, E., Joyce, N., Apkon, S., Richardson, R.C., McDonald, Craig M., Meier, Thomas, Voit, Thomas, Schara, Ulrike, Straathof, Chiara S.M., D'Angelo, M. Grazia, Bernert, Günther, Cuisset, Jean-Marie, Finkel, Richard S., Goemans, Nathalie, Rummey, Christian, Leinonen, Mika, Spagnolo, Paolo, and Buyse, Gunnar M.

Published
2016
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4. Deflazacort vs prednisone treatment for Duchenne muscular dystrophy: A meta‐analysis of disease progression rates in recent multicenter clinical trials

Author

McDonald CM, A238., Sajeev, G, Yao, Z, Mcdonnell, E, Elfring, G, Souza, M, Peltz, Sw, Darras, Bt, Shieh, Pb, Cox, Da, Landry, J, Signorovitch, J, Campbell, C, Torricelli, Re, Finkel, Rs, Flanigan, Km, Goemans, N, Heydemann, P, Kaminska, A, Kirschner, J, Muntoni, F, Osorio, An, Schara, U, Sejersen, T, Sweeney, Hl, Topaloglu, H, Tulinius, M, Vilchez, Jj, Voit, T, Wong, B, Alfano, Ln, Eagle, M, James, Mk, Lowes, L, Mayhew, A, Mazzone, Es, Nelson, L, Rose, Kj, Abdel-Hamid, Hz, Apkon, Sd, Barohn, Rj, Bertini, E, Bloetzer, C, de Vaud LC, Butterfield, Rj, Chabrol, B, Chae, Jh, Jongno-Gu, Dr, Comi, Gp, Dastgir, J, Desguerre, I, Escobar, Rg, Finanger, E, Guglieri, M, Hughes, I, Iannaccone, St, Jones, Kj, Karachunski, P, Kudr, M, Lotze, T, Mah, Jk, Mathews, K, Nevo, Y, Parsons, J, Péréon, Y, de Queiroz Campos Araujo AP, Renfroe, Jb, de Mbd, R, Ryan, M, Selby, K, Tennekoon, G, Vita, G, Abdel-Hamid, H, Apkon, S, Barohn, R, Belousova, E, Brandsema, J, Bruno, C, Burnette, W, Butterfield, R, Byrne, B, Carlo, J, Chandratre, S, Comi, G, Connolly, A, De Groot, I, Deconinck, N, Dooley, J, Dubrovsky, A, Durigneux, J, Finkel, R, Frank, Lm, Harper, A, Hattori, A, Herguner, O, Iannaccone, S, Janas, J, Jong, Yj, Komaki, H, Kuntz, N, Lee, Wt, Leung, E, Mah, J, Cm, M, Mercuri, E, Mcmillan, H, Mueller-Felber, W, Lopez de Munain, A, Nakamura, A, Niks, E, Ogata, K, Pascual, S, Pegoraro, E, Pereon, Y, Renfroe, B, Sanka, Rb, Schallner, J, Sendra, Ii, Servais, L, Smith, E, Sparks, S, Victor, R, Wicklund, M, Wilichoswki, E, and Wong, B.

Subjects
Male, Duchenne muscular dystrophy, 0301 basic medicine, medicine.medical_specialty, Physiology, medicine.drug_class, Prednisolone, Anti-Inflammatory Agents, Walking, 030105 genetics & heredity, Placebo, prednisone/prednisolone, ambulatory function, deflazacort, meta-analysis, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Pregnenediones, Prednisone, Physiology (medical), Internal medicine, Humans, Multicenter Studies as Topic, Medicine, Child, Clinical Research Articles, Randomized Controlled Trials as Topic, Clinical Research Article, business.industry, medicine.disease, Confidence interval, Muscular Dystrophy, Duchenne, Deflazacort, Treatment Outcome, meta‐analysis, Ambulatory, Disease Progression, Corticosteroid, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Abstract

Introduction In this study we characterized disease progression over 48 weeks among boys receiving deflazacort vs prednisone/prednisolone placebo arm treatment in two recent Duchenne muscular dystrophy (DMD) clinical trials. Methods Ambulatory boys with DMD receiving placebo in the phase 3 ataluren (N = 115) and tadalafil (N = 116) trials were included. The trials required at least 6 months of prior corticosteroid use and stable baseline dosing. Associations between corticosteroid use and 48‐week changes in ambulatory function were estimated using mixed models. Adjusted differences between corticosteroid groups were pooled in a meta‐analysis. Results In the meta‐analysis, deflazacort‐treated patients vs prednisone/prednisolone‐treated patients experienced, on average, lower declines of 28.3 meters on 6‐minute walk distance (95% confidence interval [CI], 5.7, 50.9; 2.9 seconds on rise from supine [95% CI, 0.9, 4.9 seconds]; 2.3 seconds on 4‐stair climb [95% CI, 0.5, 4.1 seconds]; and 2.9 [95% CI, 0.1, 5.8] points on the North Star Ambulatory Assessment linearized score). Discussion Deflazacort‐treated patients experienced significantly lower functional decline over 48 weeks.

Published
2019
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7. SMA – THERAPY

Author

Chand, D., primary, Finkel, R., additional, Day, J., additional, Darris, B., additional, Kuntz, N., additional, Connolly, A., additional, Zaidman, C., additional, Crawford, T., additional, Butterfield, R., additional, Shieh, P., additional, Tennekoon, G., additional, Brandesma, J., additional, Iannaccone, S., additional, Meriggioli, M., additional, Tauscher-Wisniewski, S., additional, Shoffner, J., additional, Ogrinc, F., additional, Kavanagh, S., additional, Feltner, D., additional, and Mendell, J., additional

Published
2020
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8. DMD – THERAPY

Author

Finanger, E., primary, Finkel, R., additional, Tennekoon, G., additional, Vandenborne, K., additional, Sweeney, L., additional, Shieh, P., additional, Yum, S., additional, Mancini, M., additional, MacDougall, J., additional, and Donovan, J., additional

Published
2020
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9. CONGENITAL MYOPATHIES 1 – NEMALINE

Author

Foley, A., primary, Ferranti, S., additional, Saade, D., additional, Mohassel, P., additional, Donkervoort, S., additional, Medne, L., additional, Dastgir, J., additional, Bharucha-Goebel, D., additional, Meilleur, K., additional, Leach, M., additional, Scavina, M., additional, Yum, S., additional, Tennekoon, G., additional, and Bönnemann, C., additional

Published
2020
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11. Towards regulatory endorsement of drug development tools to promote the application of model-informed drug development in Duchenne muscular dystrophy

Author

Conrado, D. J., Larkindale, J., Berg, A., Hill, M., Burton, J., Abrams, K. R., Abresch, R. T., Bronson, A., Chapman, D., Crowther, M., Duong, T., Gordish-Dressman, H., Harnisch, L., Henricson, E., Kim, S., Mcdonald, C. M., Schmidt, S., Vong, C., Wang, X., Wong, B. L., Yong, F., Romero, K., Vishwanathan, V., Chidambaranathan, S., Douglas Biggar, W., Mcadam, L. C., Mah, J. K., Tulinius, M., Cnaan, A., Morgenroth, L. P., Leshner, R., Tesi-Rocha, C., Thangarajh, M., Kornberg, A., Ryan, M., Nevo, Y., Dubrovsky, A., Clemens, P. R., Abdel-Hamid, H., Connolly, A. M., Pestronk, A., Teasley, J., Bertorini, T. E., Webster, R., Kolski, H., Kuntz, N., Driscoll, S., Bodensteiner, J. B., Gorni, K., Lotze, T., Day, J. W., Karachunski, P., Henricson, E. K., Joyce, N. C., Campbell, C., Torricelli, R. E., Finkel, R. S., Flanigan, K. M., Goemans, N., Heydemann, P., Kaminska, A., Kirschner, J., Muntoni, F., Osorio, A. N., Schara, U., Sejersen, T., Shieh, P. B., Sweeney, H. L., Topaloglu, H., Vilchez, J. J., Voit, T., Wong, B., Alfano, L. N., Eagle, M., James, M. K., Lowes, L., Mayhew, A., Mazzone, E. S., Nelson, L., Rose, K. J., Abdel-Hamid, H. Z., Apkon, S. D., Barohn, R. J., Bertini, E., Bloetzer, C., Devaud, L. C., Butterfield, R. J., Chabrol, B., Chae, J. H., Jongno-Gu, D. R., Comi, G. P., Darras, B. T., Dastgir, J., Desguerre, I., Escobar, R. G., Finanger, E., Guglieri, M., Hughes, I., Iannaccone, S. T., Jones, K. J., Kudr, M., Mathews, K., Parsons, J., Pereon, Y., de Queiroz Campos Araujo, A. P., Renfroe, J. B., de Resende, M. B. D., Selby, K., Tennekoon, G., Vita, G., Apkon, S., Barohn, R., Belousova, E., Brandsema, J., Bruno, C., Burnette, W., Butterfield, R., Byrne, B., Carlo, J., Chandratre, S., Comi, G., Connolly, A., De Groot I, I., Deconinck, N., Dooley, J., Durigneux, J., Finkel, R., Frank, L. M., Harper, A., Hattori, A., Herguner, O., Iannaccone, S., Janas, J., Jong, Y. J., Komaki, H., Lee, W. T., Leung, E., Mah, J., Mercuri, E., Mcmillan, H., Mueller-Felber, W., de Munain A, L., Nakamura, A., Niks, E., Ogata, K., Pascual, S., Pegoraro, E., Renfroe, B., Sanka, R. B., Schallner, J., Sendra, I. I., Servais, L., Smith, E., Sparks, S., Victor, R., Wicklund, M., Wilichoswki, E., Carter, G. T., and Servais, LJP

Subjects
Orphan Drug Production, Duchenne muscular dystrophy, Pharmacy, Model-informed drug development, 030226 pharmacology & pharmacy, Models, Biological, Food and drug administration, 03 medical and health sciences, 0302 clinical medicine, Models, medicine, Humans, Regulatory science, Computer Simulation, Muscular Dystrophy, Drug development tools, Duchenne muscular dystrophy consortium (D-RSC), Rare diseases, Regulatory endorsement, Clinical Trials as Topic, Muscular Dystrophy, Duchenne, United States, United States Food and Drug Administration, Pharmacology, Protocol (science), business.industry, Duchenne, Biological, medicine.disease, Clinical trial, Risk analysis (engineering), Drug development, 030220 oncology & carcinogenesis, Aggregate data, Business
Abstract

Drug development for rare diseases is challenged by small populations and limited data. This makes development of clinical trial protocols difficult and contributes to the uncertainty around whether or not a potential therapy is efficacious. The use of data standards to aggregate data from multiple sources, and the use of such integrated databases to develop statistical models can inform protocol development and reduce the risks in developing new therapies. Achieving regulatory endorsement of such models through defined pathways at the US Food and Drug Administration and European Medicines Authority allows such tools to be used by the drug development community for defined contexts of use without further need for discussion of the underlying model(s). The Duchenne Regulatory Science Consortium (D-RSC) has brought together multiple stakeholders to develop a clinical trial simulation tool for Duchenne muscular dystrophy using such an approach. Here we describe the work of D-RSC as an example of how such an approach may be effective at reducing uncertainty in drug development for rare diseases, and thus bringing effective therapies to patients faster.

Published
2019

12. O.40Intrathecal administration of onasemnogene abeparvovec gene-replacement therapy (GRT) for spinal muscular atrophy type 2 (SMA2): phase 1/2a study (STRONG)

Author

Finkel, R., primary, Day, J., additional, Darras, B., additional, Kuntz, N., additional, Connolly, A., additional, Crawford, T., additional, Butterfield, R., additional, Shieh, P., additional, Tennekoon, G., additional, Iannaccone, S., additional, Ogrinc, F., additional, Kavanagh, S., additional, Kernbauer, E., additional, Whittle, J., additional, L'Italien, J., additional, Kaspar, B., additional, Sproule, D., additional, Spector, S., additional, Feltner, D., additional, and Mendell, J., additional

Published
2019
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13. Intrathecal administration of AVXS-101 gene-replacement therapy (GRT) for spinal muscular atrophy type 2 (SMA2): Phase 1/2A study (strong)

Author

Finkel, R.S., primary, Day, J.W., additional, Darras, B.T., additional, Kuntz, N.L., additional, Connolly, A.M., additional, Crawford, T.O., additional, Butterfield, R.J., additional, Shieh, P.B., additional, Tennekoon, G., additional, Iannaccone, S.T., additional, Meriggioli, M., additional, Ogrinc, F.G., additional, Kavanagh, S., additional, Kernbauer, E., additional, Whittle, J., additional, L'Italien, J., additional, Kaspar, B., additional, Sproule, D.M., additional, Spector, S.A., additional, Feltner, D.E., additional, and Mendell, J.R., additional

Published
2019
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14. O.42Treatment of young boys with Duchenne muscular dystrophy with the NF-κB inhibitor edasalonexent showed a slowing of disease progression as assessed by MRI and functional measures

Author

Finkel, R., primary, Vandenborne, K., additional, Sweeney, H., additional, Finanger, E., additional, Tennekoon, G., additional, Shieh, P., additional, Willcocks, R., additional, Walter, G., additional, Rooney, W., additional, Forbes, S., additional, Triplett, W., additional, Yum, S., additional, Mancini, M., additional, MacDougall, J., additional, Fretzen, A., additional, Bista, P., additional, Nichols, A., additional, and Donovan, J., additional

Published
2019
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17. DUCHENNE MUSCULAR DYSTROPHY – IMAGING AND BIOMARKERS

Author

Forbes, S., primary, Willcocks, R., additional, Triplett, W., additional, Arora, H., additional, Rooney, W., additional, Wang, D., additional, Daniels, M., additional, Finanger, E., additional, Finkel, R., additional, Tennekoon, G., additional, Sweeney, H., additional, Walter, G., additional, and Vandenborne, K., additional

Published
2018
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18. DUCHENNE MUSCULAR DYSTROPHY - PHYSIOTHERAPY

Author

Arora, H., primary, Willcocks, R., additional, Forbes, S., additional, Triplett, W., additional, Rooney, W., additional, Wang, D., additional, Daniels, M., additional, Finanger, E., additional, Tennekoon, G., additional, Brandsema, J., additional, Sweeney, H., additional, Walter, G., additional, and Vandenborne, K., additional

Published
2018
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19. DMD CLINICAL THERAPIES I

Author

Richard, F., primary, Vandenborne, K., additional, Sweeney, H., additional, Finanger, E., additional, Tennekoon, G., additional, Shieh, P., additional, Willcocks, R., additional, Walter, G., additional, Rooney, W., additional, Forbes, S., additional, Triplett, W., additional, Yum, S., additional, Mancini, M., additional, MacDougall, J., additional, Fretzen, A., additional, Bista, P., additional, Nichols, A., additional, and Donovan, J., additional

Published
2018
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20. Ambulatory function in spinal muscular atrophy: Age-related patterns of progression.

Author

Montes, J, Mcdermott, Mp, Mirek, E, Mazzone, Elena Stacy, Main, M, Glanzman, Am, Duong, T, Young, Sd, Salazar, R, Pasternak, A, Gee, R, De Sanctis, R, Coratti, Giorgia, Forcina, N, Fanelli, L, Ramsey, D, Milev, E, Civitello, M, Pane, Marika, Pera, Maria Carmela, Scoto, M, Day, Jw, Tennekoon, G, Finkel, R, Darras, Bt, Muntoni, F, De Vivo, Dc, Mercuri, Eugenio Maria, Mazzone ES, Coratti G (ORCID:0000-0001-6666-5628), Pane M (ORCID:0000-0002-4851-6124), Pera MC (ORCID:0000-0001-6777-1721), Mercuri E. (ORCID:0000-0002-9851-5365), Montes, J, Mcdermott, Mp, Mirek, E, Mazzone, Elena Stacy, Main, M, Glanzman, Am, Duong, T, Young, Sd, Salazar, R, Pasternak, A, Gee, R, De Sanctis, R, Coratti, Giorgia, Forcina, N, Fanelli, L, Ramsey, D, Milev, E, Civitello, M, Pane, Marika, Pera, Maria Carmela, Scoto, M, Day, Jw, Tennekoon, G, Finkel, R, Darras, Bt, Muntoni, F, De Vivo, Dc, Mercuri, Eugenio Maria, Mazzone ES, Coratti G (ORCID:0000-0001-6666-5628), Pane M (ORCID:0000-0002-4851-6124), Pera MC (ORCID:0000-0001-6777-1721), and Mercuri E. (ORCID:0000-0002-9851-5365)

Abstract

Individuals with spinal muscular atrophy (SMA) type 3 are able to walk but they have weakness, gait impairments and fatigue. Our primary study objective was to examine longitudinal changes in the six-minute walk test (6MWT) and to evaluate whether age and SMA type 3 subtype are associated with decline in ambulatory function. Data from three prospective natural history studies were used. Seventy-three participants who performed the 6MWT more than once, at least 6 months apart, were included; follow-up ranged from 0.5-9 years. Only data from patients who completed the 6MWT were included. The mean age of the participants was 13.5 years (range 2.6-49.1), with 52 having disease onset before age 3 years (type 3A). At baseline, type 3A participants walked a shorter distance on average (257.1 m) than type 3B participants (390.2 m) (difference = 133.1 m, 95% confidence interval [CI] 71.8-194.3, p < 0.001). Distance walked was weakly associated with age (r = 0.25, p = 0.04). Linear mixed effects models were used to estimate the mean annual rate of change. The overall mean rate of change was -7.8 m/year (95% CI -13.6 --2.0, p = 0.009) and this did not differ by subtype (type 3A: -8.5 m/year, type 3B: -6.6 m/year, p = 0.78), but it did differ by age group (< 6: 9.8 m/year; 6-10: -7.9 m/year; 11-19: -20.8 m/year; ≥ 20: -9.7 m/year; p = 0.005). Our results showed an overall decline on the 6MWT over time, but different trajectories were observed depending on age. Young ambulant SMA patients gain function but in adolescence, patients lose function. Future clinical trials in ambulant SMA patients should consider in their design the different trajectories of ambulatory function over time, based on age.

Published
2018

21. Evaluator Training and Reliability for SMA Global Nusinersen Trials1.

Author

Glanzman, Am, Mazzone, Elena Stacy, Young, Sd, Gee, R, Rose, K, Mayhew, A, Nelson, L, Yun, C, Alexander, K, Darras, Bt, Zolkipli-Cunningham, Z, Tennekoon, G, Day, Jw, Finkel, R, Mercuri, Eugenio Maria, De Vivo, Dc, Baldwin, R, Bishop, Km, Montes, J., Mercuri E (ORCID:0000-0002-9851-5365), Glanzman, Am, Mazzone, Elena Stacy, Young, Sd, Gee, R, Rose, K, Mayhew, A, Nelson, L, Yun, C, Alexander, K, Darras, Bt, Zolkipli-Cunningham, Z, Tennekoon, G, Day, Jw, Finkel, R, Mercuri, Eugenio Maria, De Vivo, Dc, Baldwin, R, Bishop, Km, Montes, J., and Mercuri E (ORCID:0000-0002-9851-5365)

Abstract

BACKGROUND: Training methodology was established to optimize reliability of outcome measures in the nusinersen clinical trials. The Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND), Hammersmith Functional Motor Scale Expanded (HFMSE), and Revised Upper Limb (RULM) were primary or secondary outcomes. METHODS: Video review, quarterly conference calls, and item scoring checks supported evaluator competence. Baseline and screening along with video review established intra and inter-rater reliability. RESULTS: Inter and intra-rater reliability were both excellent. Intraclass correlation coefficients (ICC) ranged between 0.906-0.994 across initial training meetings and 0.824-0.996 across annual retraining meetings. This was similar for CHOP INTEND (ICC = 0.824-0.951), HFMSE (ICC = 0.981-0.996), and RULM (ICC = 0.966-0.990). Intra-rater reliability for the CHOP INTEND, HFMSE, and RULM were ICC = 0.895 (95% CI: 0.852-0.926; n = 116), ICC = 0.959 (95% CI: 0.942-0.971; n = 125), and ICC = 0.948 (95% CI: 0.927-0.963; n = 126) respectively. CONCLUSIONS: Rigorous evaluator training ensures reliability of assessment of subjects with spinal muscular atrophy (SMA) in multicenter international trials.

Published
2018

24. Treatment effect of idebenone on inspiratory function in patients with Duchenne muscular dystrophy

Author

Buyse, G.M., Voit, Thomas, Schara, Ulrike, Straathof, C.S.M., D’Angelo, M.G., Bernert, G., Cuisset, J.-M., Finkel, Richard S., Goemans, N., Rummey, Christian, Leinonen, Mika, Mayer, Oscar H., Spagnolo, Paolo, Meier, Thomas, McDonald, Craig M., Knipp, F., Van den Hauwe, M., Doppler, V., Gidaro, T., Coopman, S., Lutz, S., Kirschner, J., Borell, S., Will, M., Brighina, E., Gandossini, S., Gorni, K., Falcier, E., Politano, L., D’Ambrosio, P., Taglia, A., Verschuuren, J.J.G.M., Vílchez Padilla, J.J., Muelas Gómez, N., Sejersen, T., Hovmöller, M., Jeannet, P.-Y., Bloetzer, C., Iannaccone, S., Castro, D., Tennekoon, G., Bönnemann, C., Henricson, E., Joyce, N., Apkon, S., Richardson, R.C., and Van den Hauwe, M

Subjects
0301 basic medicine, Male, Ubiquinone, Duchenne muscular dystrophy, Medizin, Pediatrics, Antioxidants, Pulmonary function testing, law.invention, 0302 clinical medicine, Randomized controlled trial, law, respiratory function, Idebenone, Respiratory function, Lung volumes, Muscular Dystrophy, Child, Genetics (clinical), Respiration, Perinatology and Child Health, Inspiratory flow, Pediatrics, Perinatology and Child Health, Pulmonary and Respiratory Medicine, 3. Good health, Respiratory Function Tests, Treatment Outcome, Neurology, Cardiology, Inspiratory Reserve Volume, inspiratory flow, Female, Original Article, medicine.drug, medicine.medical_specialty, Adolescent, Outcomes, Placebo, 03 medical and health sciences, FEV1/FVC ratio, Internal medicine, medicine, Humans, Treatment effect, In patient, business.industry, Original Articles, idebenone, Muscular Dystrophy, Duchenne, Duchenne, medicine.disease, Surgery, 030104 developmental biology, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Assessment of dynamic inspiratory function may provide valuable information about the degree and progression of pulmonary involvement in patients with Duchenne muscular dystrophy (DMD). The aims of this study were to characterize inspiratory function and to assess the efficacy of idebenone on this pulmonary function outcome in a large and well-characterized cohort of 10-18 year-old DMD patients not taking glucocorticoid steroids (GCs) enrolled in the phase 3 randomized controlled DELOS trial. We evaluated the effect of idebenone on the highest flow generated during an inspiratory FVC maneuver (maximum inspiratory flow; V'I,max(FVC)) and the ratio between the largest inspiratory flow during tidal breathing (tidal inspiratory flow; V'I,max(t)) and the V'I,max(FVC). The fraction of the maximum flow that is not used during tidal breathing has been termed inspiratory flow reserve (IFR). DMD patients in both treatment groups of DELOS (idebenone, n = 31; placebo: n = 33) had comparable and abnormally low V'I,max(FVC) at baseline. During the study period, V'I,max(FVC) further declined by -0.29 L/sec in patients on placebo (95%CI: -0.51, -0.08; P = 0.008 at week 52), whereas it remained stable in patients on idebenone (change from baseline to week 52: 0.01 L/sec; 95%CI: -0.22, 0.24; P = 0.950). The between-group difference favoring idebenone was 0.27 L/sec (P = 0.043) at week 26 and 0.30 L/sec (P = 0.061) at week 52. In addition, during the study period, IFR improved by 2.8% in patients receiving idebenone and worsened by -3.0% among patients on placebo (between-group difference 5.8% at week 52; P = 0.040). Although the clinical interpretation of these data is currently limited due to the scarcity of routine clinical practice experience with dynamic inspiratory function outcomes in DMD, these findings from a randomized controlled study nevertheless suggest that idebenone preserved inspiratory muscle function as assessed by V'I,max(FVC) and IFR in patients with DMD. Pediatr Pulmonol. © 2016 The Authors. Pediatric Pulmonology Published by Wiley Periodicals, Inc. ispartof: Pediatric Pulmonology vol:52 issue:4 pages:508-515 ispartof: location:United States status: published

Published
2016

26. Magnetic resonance biomarkers in the proximal and distal upper extremity in a large cohort of boys with Duchenne muscular dystrophy

Author

Willcocks, R., primary, Forbes, S., additional, Lott, D., additional, Senesac, C., additional, Arora, H., additional, Barnard, A., additional, Harrington, A., additional, Daniels, M., additional, Finanger, E., additional, Tennekoon, G., additional, Finkel, R., additional, Wang, D., additional, Rooney, W., additional, Walter, G., additional, Sweeney, H., additional, and Vandenborne, K., additional

Published
2017
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27. MoveDMD: phase 2 trial of edasalonexent, an NF-κB inhibitor, in 4 to 7-year old patients with Duchenne muscular dystrophy

Author

Finkel, R., primary, Vandenborne, K., additional, Sweeney, H., additional, Finanger, E., additional, Tennekoon, G., additional, Shieh, P., additional, Willcocks, R., additional, Forbes, S., additional, Triplett, W., additional, Yum, S., additional, Mancini, M., additional, Friedman, M., additional, Fretzen, A., additional, and Donovan, J., additional

Published
2017
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28. Characterization of pulmonary function in 10–18 year old patients with Duchenne muscular dystrophy

Author

Meier, Thomas, primary, Rummey, Christian, additional, Leinonen, Mika, additional, Spagnolo, Paolo, additional, Mayer, Oscar H., additional, Buyse, Gunnar M., additional, Bernert, G., additional, Knipp, F., additional, Buyse, G.M., additional, Goemans, N., additional, Van den Hauwe, M., additional, Voit, T., additional, Doppler, V., additional, Gidaro, T., additional, Cuisset, J.-M., additional, Coopman, S., additional, Schara, U., additional, Lutz, S., additional, Kirschner, J., additional, Borell, S., additional, Will, M., additional, D'Angelo, M.G., additional, Brighina, E., additional, Gandossini, S., additional, Gorni, K., additional, Falcier, E., additional, Politano, L., additional, D'Ambrosio, P., additional, Taglia, A., additional, Verschuuren, J.J.G.M., additional, Straathof, C.S.M., additional, Vílchez Padilla, J.J., additional, Muelas Gómez, N., additional, Sejersen, T., additional, Hovmöller, M., additional, Jeannet, P.-Y., additional, Bloetzer, C., additional, Iannaccone, S., additional, Castro, D., additional, Tennekoon, G., additional, Finkel, R., additional, Bönnemann, C., additional, McDonald, C., additional, Henricson, E., additional, Joyce, N., additional, Apkon, S., additional, and Richardson, R.C., additional

Published
2017
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29. Ataluren in patients with nonsense mutation Duchenne muscular dystrophy (ACT DMD): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial

Author

McDonald, C. M., Campbell, C., Torricelli, R. E., Finkel, R. S., Flanigan, K. M., Goemans, N., Heydemann, P., Kaminska, A., Kirschner, J., Muntoni, F., Osorio, A. N., Schara, U., Sejersen, T., Shieh, P. B., Sweeney, H. L., Topaloglu, H., Tulinius, M., Vilchez, J. J., Voit, T., Wong, B., Elfring, G., Kroger, H., Luo, X., McIntosh, J., Ong, T., Riebling, P., Souza, M., Spiegel, R. J., Peltz, S. W., Mercuri, E., Alfano, L. N., Eagle, M., James, M. K., Lowes, L., Mayhew, A., Mazzone, E. S., Nelson, L., Rose, K. J., Abdel-Hamid, H. Z., Apkon, S. D., Barohn, R. J., Bertini, E., Bloetzer, C., de Vaud, L. C., Butterfield, R. J., Chabrol, B., Chae, J. -H., Jongno-gu, D. -R., Comi, G. P., Darras, B. T., Dastgir, J., Desguerre, I., Escobar, R. G., Finanger, E., Guglieri, M., Hughes, I., Iannaccone, S. T., Jones, K. J., Karachunski, P., Kudr, M., Lotze, T., Mah, J. K., Mathews, K., Nevo, Y., Parsons, J., Pereon, Y., de Queiroz Campos Araujo, A. P., Renfroe, J. B., de Resende, M. B. D., Ryan, M., Selby, K., Tennekoon, G., Vita, G., Mercuri E. (ORCID:0000-0002-9851-5365), McDonald, C. M., Campbell, C., Torricelli, R. E., Finkel, R. S., Flanigan, K. M., Goemans, N., Heydemann, P., Kaminska, A., Kirschner, J., Muntoni, F., Osorio, A. N., Schara, U., Sejersen, T., Shieh, P. B., Sweeney, H. L., Topaloglu, H., Tulinius, M., Vilchez, J. J., Voit, T., Wong, B., Elfring, G., Kroger, H., Luo, X., McIntosh, J., Ong, T., Riebling, P., Souza, M., Spiegel, R. J., Peltz, S. W., Mercuri, E., Alfano, L. N., Eagle, M., James, M. K., Lowes, L., Mayhew, A., Mazzone, E. S., Nelson, L., Rose, K. J., Abdel-Hamid, H. Z., Apkon, S. D., Barohn, R. J., Bertini, E., Bloetzer, C., de Vaud, L. C., Butterfield, R. J., Chabrol, B., Chae, J. -H., Jongno-gu, D. -R., Comi, G. P., Darras, B. T., Dastgir, J., Desguerre, I., Escobar, R. G., Finanger, E., Guglieri, M., Hughes, I., Iannaccone, S. T., Jones, K. J., Karachunski, P., Kudr, M., Lotze, T., Mah, J. K., Mathews, K., Nevo, Y., Parsons, J., Pereon, Y., de Queiroz Campos Araujo, A. P., Renfroe, J. B., de Resende, M. B. D., Ryan, M., Selby, K., Tennekoon, G., Vita, G., and Mercuri E. (ORCID:0000-0002-9851-5365)

Abstract

Background Duchenne muscular dystrophy (DMD) is a severe, progressive, and rare neuromuscular, X-linked recessive disease. Dystrophin deficiency is the underlying cause of disease; therefore, mutation-specific therapies aimed at restoring dystrophin protein production are being explored. We aimed to assess the efficacy and safety of ataluren in ambulatory boys with nonsense mutation DMD. Methods We did this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at 54 sites in 18 countries located in North America, Europe, the Asia-Pacific region, and Latin America. Boys aged 7–16 years with nonsense mutation DMD and a baseline 6-minute walk distance (6MWD) of 150 m or more and 80% or less of the predicted normal value for age and height were randomly assigned (1:1), via permuted block randomisation (block size of four) using an interactive voice-response or web-response system, to receive ataluren orally three times daily (40 mg/kg per day) or matching placebo. Randomisation was stratified by age (<9 years vs ≥9 years), duration of previous corticosteroid use (6 months to <12 months vs ≥12 months), and baseline 6MWD (<350 m vs ≥350 m). Patients, parents and caregivers, investigational site personnel, PTC Therapeutics employees, and all other study personnel were masked to group allocation until after database lock. The primary endpoint was change in 6MWD from baseline to week 48. We additionally did a prespecified subgroup analysis of the primary endpoint, based on baseline 6MWD, which is reflective of anticipated rates of disease progression over 1 year. The primary analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01826487. Findings Between March 26, 2013, and Aug 26, 2014, we randomly assigned 230 patients to receive ataluren (n=115) or placebo (n=115); 228 patients comprised the intention-to-treat population. The least-squares mean change in 6MWD from baseline to week 48 was −47·7 m (SE 9·3

Published
2017

30. Should motor function determine the timing of scoliosis surgery in spinal muscular atrophy?

Author

Dunaway Young, S., primary, Montes, J., additional, Salazar, R., additional, Glanzman, A., additional, Pasternak, A., additional, Quigley, J., additional, Ciurylo, E., additional, Riley, S., additional, Martens, W., additional, Gee, R., additional, Duong, T., additional, Civitello, M., additional, Chiriboga, C., additional, Tennekoon, G., additional, Day, J., additional, Finkel, R., additional, Darras, B., additional, and De Vivo, D., additional

Published
2016
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32. Idebenone reduces respiratory complications in patients with Duchenne muscular dystrophy

Author

McDonald, Craig M., primary, Meier, Thomas, additional, Voit, Thomas, additional, Schara, Ulrike, additional, Straathof, Chiara S.M., additional, D'Angelo, M. Grazia, additional, Bernert, Günther, additional, Cuisset, Jean-Marie, additional, Finkel, Richard S., additional, Goemans, Nathalie, additional, Rummey, Christian, additional, Leinonen, Mika, additional, Spagnolo, Paolo, additional, Buyse, Gunnar M., additional, Bernert, G., additional, Knipp, F., additional, Buyse, G.M., additional, Goemans, N., additional, van den Hauwe, M., additional, Voit, T., additional, Doppler, V., additional, Gidaro, T., additional, Cuisset, J.-M., additional, Coopman, S., additional, Schara, U., additional, Lutz, S., additional, Kirschner, J., additional, Borell, S., additional, Will, M., additional, D'Angelo, M.G., additional, Brighina, E., additional, Gandossini, S., additional, Gorni, K., additional, Falcier, E., additional, Politano, L., additional, D'Ambrosio, P., additional, Taglia, A., additional, Verschuuren, J.J.G.M., additional, Straathof, C.S.M., additional, Vílchez Padilla, J.J., additional, Muelas Gómez, N., additional, Sejersen, T., additional, Hovmöller, M., additional, Jeannet, P.-Y., additional, Bloetzer, C., additional, Iannaccone, S., additional, Castro, D., additional, Tennekoon, G., additional, Finkel, R., additional, Bönnemann, C., additional, McDonald, C., additional, Henricson, E., additional, Joyce, N., additional, Apkon, S., additional, and Richardson, R.C., additional

Published
2016
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33. Spinal muscular atrophy functional composite score: A functional measure in spinal muscular atrophy

Author

Montes, J., Glanzman, A. M., Mazzone, Elena Stacy, Martens, W. B., Dunaway, S., Pasternak, A., Riley, S. O., Quigley, J., Pandya, S., De Vivo, D. C., Kaufmann, P., Chiriboga, C. A., Finkel, R. S., Tennekoon, G. I., Darras, B. T., Pane, Marika, Mercuri, Eugenio Maria, Mcdermott, M. P., Mazzone E. S., Pane M. (ORCID:0000-0002-4851-6124), Mercuri E. (ORCID:0000-0002-9851-5365), Montes, J., Glanzman, A. M., Mazzone, Elena Stacy, Martens, W. B., Dunaway, S., Pasternak, A., Riley, S. O., Quigley, J., Pandya, S., De Vivo, D. C., Kaufmann, P., Chiriboga, C. A., Finkel, R. S., Tennekoon, G. I., Darras, B. T., Pane, Marika, Mercuri, Eugenio Maria, Mcdermott, M. P., Mazzone E. S., Pane M. (ORCID:0000-0002-4851-6124), and Mercuri E. (ORCID:0000-0002-9851-5365)

Abstract

Introduction: With clinical trials underway, our objective was to construct a composite score of global function that could discriminate among people with spinal muscular atrophy (SMA). Methods: Data were collected from 126 participants with SMA types 2 and 3. Scores from the Hammersmith Functional Motor Scale-Expanded and Upper Limb Module were expressed as a percentage of the maximum score and 6-minute walk test as percent of predicted normal distance. A principal component analysis was performed on the correlation matrix for the 3 percentage scores. Results: The first principal component yielded a composite score with approximately equal weighting of the 3 components and accounted for 82% of the total variability. The SMA functional composite score, an unweighted average of the 3 individual percentage scores, correlated almost perfectly with the first principal component. Conclusions: This combination of measures broadens the spectrum of ability that can be quantified in type 2 and 3 SMA patients.

Published
2015

34. Genetic polymorphisms modify intramuscular fat infiltration in Duchenne muscular dystrophy

Author

Barnard, A., primary, Romero de Mello Sa, S., additional, Willcocks, R., additional, Senesac, C., additional, Finkel, R., additional, Forbes, S., additional, Sweeney, H., additional, Tennekoon, G., additional, Triplett, W., additional, Lott, D., additional, Wang, D., additional, Byrne, B., additional, Hammers, D., additional, Pham, J., additional, Rooney, W., additional, Finanger, E., additional, Walter, G., additional, Vandenborne, K., additional, and Russman, B., additional

Published
2015
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37. G.P.99

Author

Estilow, T., primary, Glanzman, A., additional, Flickinger, J., additional, Powers, K.M., additional, Moll, A., additional, Medne, L., additional, Tennekoon, G., additional, and Yum, S.W., additional

Published
2014
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38. Examination of effects of corticosteroids on skeletal muscles of boys with DMD using MRI and MRS

Author

Arpan, I., primary, Willcocks, R. J., additional, Forbes, S. C., additional, Finkel, R. S., additional, Lott, D. J., additional, Rooney, W. D., additional, Triplett, W. T., additional, Senesac, C. R., additional, Daniels, M. J., additional, Byrne, B. J., additional, Finanger, E. L., additional, Russman, B. S., additional, Wang, D.-J., additional, Tennekoon, G. I., additional, Walter, G. A., additional, Sweeney, H. L., additional, and Vandenborne, K., additional

Published
2014
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43. P3.48 Exome sequencing with linkage analysis identifies a novel ACTA1 variant in a large family with progressive muscle weakness

Author

Perkins, K.Z., primary, Meilleur, K., additional, Medne, L., additional, Devoto, M., additional, Tennekoon, G., additional, Yum, S., additional, Yang, M., additional, Finkel, R., additional, Johnson, J., additional, Gibbs, J.R., additional, Ferguson, T., additional, Zou, Y., additional, Traynor, B., additional, and Bonnemann, C., additional

Published
2011
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