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1. From the Manpower Revolution to the Activation Paradigm

Author

Weishaupt, J. Timo

Subjects
public administration, sociology, bestuurskunde, sociologie, bic Book Industry Communication::J Society & social sciences::JF Society & culture: general::JFF Social issues & processes, bic Book Industry Communication::J Society & social sciences::JH Sociology & anthropology, bic Book Industry Communication::J Society & social sciences::JP Politics & government
Abstract

This book examines the origins and evolution of labor market policy in Western Europe, while paying close attention to the oeCD and the European Union as proliferators of new ideas. Three phases are identified: (a) a manpower revolution phase during the 1960s and 1970s, when most European governments emulated Swedish manpower policies and introduced/modernized their public employment services; (b) a phase of international disagreement about the root causes of, and remedies for, unemployment, triggering a diversity of policy responses during the late 1970s and 1980s; and (c) the emergence of an activation paradigm since the late 1990s, causing a process of institutional hybridization. The book's main contention is that the evolution of labor market policy is not only determined by historical trajectories or coalitional struggles, but also by policy makers' changing normative and cognitive beliefs. The cases studied include Austria, Denmark, Germany, Ireland, Sweden, and the United Kingdom., In dit boek onderzoekt J. Timo Weishaupt de oorsprong en evolutie van de arbeidsmarkt en arbeidswetgeving in West-Europa. Extra aandacht gaat daarbij uit naar de oeCD en de Europese Unie als voortrekkers van nieuwe ideeën op dit gebied. Timo Weishaupt deed onderzoek in Oostenrijk, Denemarken, Duitsland, Ierland, Zweden en het Verenigd Koninkrijk. Hij komt tot de conclusie dat de evolutie van arbeidswetgeving niet alleen wordt bepaald door historische ontwikkelingen, maar ook door de veranderende overtuigingen van beleidsmakers.

Published
2011
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19. Author Correction: Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology (Nature Genetics, (2021), 53, 12, (1636-1648), 10.1038/s41588-021-00973-1)

Author

van Rheenen W., van Rheenen, W, van der Spek, R, Bakker, M, van Vugt, J, Hop, P, Zwamborn, R, de Klein, N, Westra, H, Bakker, O, Deelen, P, Shireby, G, Hannon, E, Moisse, M, Baird, D, Restuadi, R, Dolzhenko, E, Dekker, A, Gawor, K, Westeneng, H, Tazelaar, G, van Eijk, K, Kooyman, M, Byrne, R, Doherty, M, Heverin, M, Al Khleifat, A, Iacoangeli, A, Shatunov, A, Ticozzi, N, Cooper-Knock, J, Smith, B, Gromicho, M, Chandran, S, Pal, S, Morrison, K, Shaw, P, Hardy, J, Orrell, R, Sendtner, M, Meyer, T, Basak, N, van der Kooi, A, Ratti, A, Fogh, I, Gellera, C, Lauria, G, Corti, S, Cereda, C, Sproviero, D, D'Alfonso, S, Soraru, G, Siciliano, G, Filosto, M, Padovani, A, Chio, A, Calvo, A, Moglia, C, Brunetti, M, Canosa, A, Grassano, M, Beghi, E, Pupillo, E, Logroscino, G, Nefussy, B, Osmanovic, A, Nordin, A, Lerner, Y, Zabari, M, Gotkine, M, Baloh, R, Bell, S, Vourc'H, P, Corcia, P, Couratier, P, Millecamps, S, Meininger, V, Salachas, F, Mora Pardina, J, Assialioui, A, Rojas-Garcia, R, Dion, P, Ross, J, Ludolph, A, Weishaupt, J, Brenner, D, Freischmidt, A, Bensimon, G, Brice, A, Durr, A, Payan, C, Saker-Delye, S, Wood, N, Topp, S, Rademakers, R, Tittmann, L, Lieb, W, Franke, A, Ripke, S, Braun, A, Kraft, J, Whiteman, D, Olsen, C, Uitterlinden, A, Hofman, A, Rietschel, M, Cichon, S, Nothen, M, Amouyel, P, Comi, G, Riva, N, Lunetta, C, Gerardi, F, Cotelli, M, Rinaldi, F, Chiveri, L, Guaita, M, Perrone, P, Ceroni, M, Diamanti, L, Ferrarese, C, Tremolizzo, L, Delodovici, M, Bono, G, Manera, U, Vasta, R, Bombaci, A, Casale, F, Fuda, G, Salamone, P, Iazzolino, B, Peotta, L, Cugnasco, P, De Marco, G, Torrieri, M, Palumbo, F, Gallone, S, Barberis, M, Sbaiz, L, Gentile, S, Mauro, A, Mazzini, L, De Marchi, F, Corrado, L, Bertolotto, A, Gionco, M, Leotta, D, Odddenino, E, Imperiale, D, Cavallo, R, Pignatta, P, De Mattei, M, Geda, C, Papurello, D, Gusmaroli, G, Comi, C, Labate, C, Ruiz, L, Ferrandi, D, Rota, E, Aguggia, M, Di Vito, N, Meineri, P, Ghiglione, P, Launaro, N, Dotta, M, Di Sapio, A, Giardini, G, Tiloca, C, Peverelli, S, Taroni, F, Pensato, V, Castellotti, B, Del Bo, R, Gagliardi, S, Raggi, F, Simoncini, C, Lo Gerfo, A, Inghilleri, M, Ferlini, A, Simone, I, Passarella, B, Guerra, V, Zoccolella, S, Nozzoli, C, Mundi, C, Leone, M, Zarrelli, M, Tamma, F, Valluzzi, F, Calabrese, G, Boero, G, Rini, A, Traynor, B, Singleton, A, Mitne Neto, M, Cauchi, R, Ophoff, R, Wiedau-Pazos, M, Lomen-Hoerth, C, van Deerlin, V, Grosskreutz, J, Roediger, A, Gaur, N, Jork, A, Barthel, T, Theele, E, Ilse, B, Stubendorff, B, Witte, O, Steinbach, R, Hubner, C, Graff, C, Brylev, L, Fominykh, V, Demeshonok, V, Ataulina, A, Rogelj, B, Koritnik, B, Zidar, J, Ravnik-Glavac, M, Glavac, D, Stevic, Z, Drory, V, Povedano, M, Blair, I, Kiernan, M, Benyamin, B, Henderson, R, Furlong, S, Mathers, S, Mccombe, P, Needham, M, Ngo, S, Nicholson, G, Pamphlett, R, Rowe, D, Steyn, F, Williams, K, Mather, K, Sachdev, P, Henders, A, Wallace, L, de Carvalho, M, Pinto, S, Petri, S, Weber, M, Rouleau, G, Silani, V, Curtis, C, Breen, G, Glass, J, Brown, R, Landers, J, Shaw, C, Andersen, P, Groen, E, van Es, M, Pasterkamp, R, Fan, D, Garton, F, Mcrae, A, Davey Smith, G, Gaunt, T, Eberle, M, Mill, J, Mclaughlin, R, Hardiman, O, Kenna, K, Wray, N, Tsai, E, Runz, H, Franke, L, Al-Chalabi, A, Van Damme, P, van den Berg, L, Veldink, J, van Rheenen W., van der Spek R. A. A., Bakker M. K., van Vugt J. J. F. A., Hop P. J., Zwamborn R. A. J., de Klein N., Westra H. -J., Bakker O. B., Deelen P., Shireby G., Hannon E., Moisse M., Baird D., Restuadi R., Dolzhenko E., Dekker A. M., Gawor K., Westeneng H. -J., Tazelaar G. H. P., van Eijk K. R., Kooyman M., Byrne R. P., Doherty M., Heverin M., Al Khleifat A., Iacoangeli A., Shatunov A., Ticozzi N., Cooper-Knock J., Smith B. N., Gromicho M., Chandran S., Pal S., Morrison K. E., Shaw P. J., Hardy J., Orrell R. W., Sendtner M., Meyer T., Basak N., van der Kooi A. J., Ratti A., Fogh I., Gellera C., Lauria G., Corti S., Cereda C., Sproviero D., D'Alfonso S., Soraru G., Siciliano G., Filosto M., Padovani A., Chio A., Calvo A., Moglia C., Brunetti M., Canosa A., Grassano M., Beghi E., Pupillo E., Logroscino G., Nefussy B., Osmanovic A., Nordin A., Lerner Y., Zabari M., Gotkine M., Baloh R. H., Bell S., Vourc'h P., Corcia P., Couratier P., Millecamps S., Meininger V., Salachas F., Mora Pardina J. S., Assialioui A., Rojas-Garcia R., Dion P. A., Ross J. P., Ludolph A. C., Weishaupt J. H., Brenner D., Freischmidt A., Bensimon G., Brice A., Durr A., Payan C. A. M., Saker-Delye S., Wood N. W., Topp S., Rademakers R., Tittmann L., Lieb W., Franke A., Ripke S., Braun A., Kraft J., Whiteman D. C., Olsen C. M., Uitterlinden A. G., Hofman A., Rietschel M., Cichon S., Nothen M. M., Amouyel P., Comi G., Riva N., Lunetta C., Gerardi F., Cotelli M. S., Rinaldi F., Chiveri L., Guaita M. C., Perrone P., Ceroni M., Diamanti L., Ferrarese C., Tremolizzo L., Delodovici M. L., Bono G., Manera U., Vasta R., Bombaci A., Casale F., Fuda G., Salamone P., Iazzolino B., Peotta L., Cugnasco P., De Marco G., Torrieri M. C., Palumbo F., Gallone S., Barberis M., Sbaiz L., Gentile S., Mauro A., Mazzini L., De Marchi F., Corrado L., Bertolotto A., Gionco M., Leotta D., Odddenino E., Imperiale D., Cavallo R., Pignatta P., De Mattei M., Geda C., Papurello D. M., Gusmaroli G., Comi C., Labate C., Ruiz L., Ferrandi D., Rota E., Aguggia M., Di Vito N., Meineri P., Ghiglione P., Launaro N., Dotta M., Di Sapio A., Giardini G., Tiloca C., Peverelli S., Taroni F., Pensato V., Castellotti B., Comi G. P., Del Bo R., Gagliardi S., Raggi F., Simoncini C., Lo Gerfo A., Inghilleri M., Ferlini A., Simone I. L., Passarella B., Guerra V., Zoccolella S., Nozzoli C., Mundi C., Leone M., Zarrelli M., Tamma F., Valluzzi F., Calabrese G., Boero G., Rini A., Traynor B. J., Singleton A. B., Mitne Neto M., Cauchi R. J., Ophoff R. A., Wiedau-Pazos M., Lomen-Hoerth C., van Deerlin V. M., Grosskreutz J., Roediger A., Gaur N., Jork A., Barthel T., Theele E., Ilse B., Stubendorff B., Witte O. W., Steinbach R., Hubner C. A., Graff C., Brylev L., Fominykh V., Demeshonok V., Ataulina A., Rogelj B., Koritnik B., Zidar J., Ravnik-Glavac M., Glavac D., Stevic Z., Drory V., Povedano M., Blair I. P., Kiernan M. C., Benyamin B., Henderson R. D., Furlong S., Mathers S., McCombe P. A., Needham M., Ngo S. T., Nicholson G. A., Pamphlett R., Rowe D. B., Steyn F. J., Williams K. L., Mather K. A., Sachdev P. S., Henders A. K., Wallace L., de Carvalho M., Pinto S., Petri S., Weber M., Rouleau G. A., Silani V., Curtis C. J., Breen G., Glass J. D., Brown R. H., Landers J. E., Shaw C. E., Andersen P. M., Groen E. J. N., van Es M. A., Pasterkamp R. J., Fan D., Garton F. C., McRae A. F., Davey Smith G., Gaunt T. R., Eberle M. A., Mill J., McLaughlin R. L., Hardiman O., Kenna K. P., Wray N. R., Tsai E., Runz H., Franke L., Al-Chalabi A., Van Damme P., van den Berg L. H., Veldink J. H., van Rheenen W., van Rheenen, W, van der Spek, R, Bakker, M, van Vugt, J, Hop, P, Zwamborn, R, de Klein, N, Westra, H, Bakker, O, Deelen, P, Shireby, G, Hannon, E, Moisse, M, Baird, D, Restuadi, R, Dolzhenko, E, Dekker, A, Gawor, K, Westeneng, H, Tazelaar, G, van Eijk, K, Kooyman, M, Byrne, R, Doherty, M, Heverin, M, Al Khleifat, A, Iacoangeli, A, Shatunov, A, Ticozzi, N, Cooper-Knock, J, Smith, B, Gromicho, M, Chandran, S, Pal, S, Morrison, K, Shaw, P, Hardy, J, Orrell, R, Sendtner, M, Meyer, T, Basak, N, van der Kooi, A, Ratti, A, Fogh, I, Gellera, C, Lauria, G, Corti, S, Cereda, C, Sproviero, D, D'Alfonso, S, Soraru, G, Siciliano, G, Filosto, M, Padovani, A, Chio, A, Calvo, A, Moglia, C, Brunetti, M, Canosa, A, Grassano, M, Beghi, E, Pupillo, E, Logroscino, G, Nefussy, B, Osmanovic, A, Nordin, A, Lerner, Y, Zabari, M, Gotkine, M, Baloh, R, Bell, S, Vourc'H, P, Corcia, P, Couratier, P, Millecamps, S, Meininger, V, Salachas, F, Mora Pardina, J, Assialioui, A, Rojas-Garcia, R, Dion, P, Ross, J, Ludolph, A, Weishaupt, J, Brenner, D, Freischmidt, A, Bensimon, G, Brice, A, Durr, A, Payan, C, Saker-Delye, S, Wood, N, Topp, S, Rademakers, R, Tittmann, L, Lieb, W, Franke, A, Ripke, S, Braun, A, Kraft, J, Whiteman, D, Olsen, C, Uitterlinden, A, Hofman, A, Rietschel, M, Cichon, S, Nothen, M, Amouyel, P, Comi, G, Riva, N, Lunetta, C, Gerardi, F, Cotelli, M, Rinaldi, F, Chiveri, L, Guaita, M, Perrone, P, Ceroni, M, Diamanti, L, Ferrarese, C, Tremolizzo, L, Delodovici, M, Bono, G, Manera, U, Vasta, R, Bombaci, A, Casale, F, Fuda, G, Salamone, P, Iazzolino, B, Peotta, L, Cugnasco, P, De Marco, G, Torrieri, M, Palumbo, F, Gallone, S, Barberis, M, Sbaiz, L, Gentile, S, Mauro, A, Mazzini, L, De Marchi, F, Corrado, L, Bertolotto, A, Gionco, M, Leotta, D, Odddenino, E, Imperiale, D, Cavallo, R, Pignatta, P, De Mattei, M, Geda, C, Papurello, D, Gusmaroli, G, Comi, C, Labate, C, Ruiz, L, Ferrandi, D, Rota, E, Aguggia, M, Di Vito, N, Meineri, P, Ghiglione, P, Launaro, N, Dotta, M, Di Sapio, A, Giardini, G, Tiloca, C, Peverelli, S, Taroni, F, Pensato, V, Castellotti, B, Del Bo, R, Gagliardi, S, Raggi, F, Simoncini, C, Lo Gerfo, A, Inghilleri, M, Ferlini, A, Simone, I, Passarella, B, Guerra, V, Zoccolella, S, Nozzoli, C, Mundi, C, Leone, M, Zarrelli, M, Tamma, F, Valluzzi, F, Calabrese, G, Boero, G, Rini, A, Traynor, B, Singleton, A, Mitne Neto, M, Cauchi, R, Ophoff, R, Wiedau-Pazos, M, Lomen-Hoerth, C, van Deerlin, V, Grosskreutz, J, Roediger, A, Gaur, N, Jork, A, Barthel, T, Theele, E, Ilse, B, Stubendorff, B, Witte, O, Steinbach, R, Hubner, C, Graff, C, Brylev, L, Fominykh, V, Demeshonok, V, Ataulina, A, Rogelj, B, Koritnik, B, Zidar, J, Ravnik-Glavac, M, Glavac, D, Stevic, Z, Drory, V, Povedano, M, Blair, I, Kiernan, M, Benyamin, B, Henderson, R, Furlong, S, Mathers, S, Mccombe, P, Needham, M, Ngo, S, Nicholson, G, Pamphlett, R, Rowe, D, Steyn, F, Williams, K, Mather, K, Sachdev, P, Henders, A, Wallace, L, de Carvalho, M, Pinto, S, Petri, S, Weber, M, Rouleau, G, Silani, V, Curtis, C, Breen, G, Glass, J, Brown, R, Landers, J, Shaw, C, Andersen, P, Groen, E, van Es, M, Pasterkamp, R, Fan, D, Garton, F, Mcrae, A, Davey Smith, G, Gaunt, T, Eberle, M, Mill, J, Mclaughlin, R, Hardiman, O, Kenna, K, Wray, N, Tsai, E, Runz, H, Franke, L, Al-Chalabi, A, Van Damme, P, van den Berg, L, Veldink, J, van Rheenen W., van der Spek R. A. A., Bakker M. K., van Vugt J. J. F. A., Hop P. J., Zwamborn R. A. J., de Klein N., Westra H. -J., Bakker O. B., Deelen P., Shireby G., Hannon E., Moisse M., Baird D., Restuadi R., Dolzhenko E., Dekker A. M., Gawor K., Westeneng H. -J., Tazelaar G. H. P., van Eijk K. R., Kooyman M., Byrne R. P., Doherty M., Heverin M., Al Khleifat A., Iacoangeli A., Shatunov A., Ticozzi N., Cooper-Knock J., Smith B. N., Gromicho M., Chandran S., Pal S., Morrison K. E., Shaw P. J., Hardy J., Orrell R. W., Sendtner M., Meyer T., Basak N., van der Kooi A. J., Ratti A., Fogh I., Gellera C., Lauria G., Corti S., Cereda C., Sproviero D., D'Alfonso S., Soraru G., Siciliano G., Filosto M., Padovani A., Chio A., Calvo A., Moglia C., Brunetti M., Canosa A., Grassano M., Beghi E., Pupillo E., Logroscino G., Nefussy B., Osmanovic A., Nordin A., Lerner Y., Zabari M., Gotkine M., Baloh R. H., Bell S., Vourc'h P., Corcia P., Couratier P., Millecamps S., Meininger V., Salachas F., Mora Pardina J. S., Assialioui A., Rojas-Garcia R., Dion P. A., Ross J. P., Ludolph A. C., Weishaupt J. H., Brenner D., Freischmidt A., Bensimon G., Brice A., Durr A., Payan C. A. M., Saker-Delye S., Wood N. W., Topp S., Rademakers R., Tittmann L., Lieb W., Franke A., Ripke S., Braun A., Kraft J., Whiteman D. C., Olsen C. M., Uitterlinden A. G., Hofman A., Rietschel M., Cichon S., Nothen M. M., Amouyel P., Comi G., Riva N., Lunetta C., Gerardi F., Cotelli M. S., Rinaldi F., Chiveri L., Guaita M. C., Perrone P., Ceroni M., Diamanti L., Ferrarese C., Tremolizzo L., Delodovici M. L., Bono G., Manera U., Vasta R., Bombaci A., Casale F., Fuda G., Salamone P., Iazzolino B., Peotta L., Cugnasco P., De Marco G., Torrieri M. C., Palumbo F., Gallone S., Barberis M., Sbaiz L., Gentile S., Mauro A., Mazzini L., De Marchi F., Corrado L., Bertolotto A., Gionco M., Leotta D., Odddenino E., Imperiale D., Cavallo R., Pignatta P., De Mattei M., Geda C., Papurello D. M., Gusmaroli G., Comi C., Labate C., Ruiz L., Ferrandi D., Rota E., Aguggia M., Di Vito N., Meineri P., Ghiglione P., Launaro N., Dotta M., Di Sapio A., Giardini G., Tiloca C., Peverelli S., Taroni F., Pensato V., Castellotti B., Comi G. P., Del Bo R., Gagliardi S., Raggi F., Simoncini C., Lo Gerfo A., Inghilleri M., Ferlini A., Simone I. L., Passarella B., Guerra V., Zoccolella S., Nozzoli C., Mundi C., Leone M., Zarrelli M., Tamma F., Valluzzi F., Calabrese G., Boero G., Rini A., Traynor B. J., Singleton A. B., Mitne Neto M., Cauchi R. J., Ophoff R. A., Wiedau-Pazos M., Lomen-Hoerth C., van Deerlin V. M., Grosskreutz J., Roediger A., Gaur N., Jork A., Barthel T., Theele E., Ilse B., Stubendorff B., Witte O. W., Steinbach R., Hubner C. A., Graff C., Brylev L., Fominykh V., Demeshonok V., Ataulina A., Rogelj B., Koritnik B., Zidar J., Ravnik-Glavac M., Glavac D., Stevic Z., Drory V., Povedano M., Blair I. P., Kiernan M. C., Benyamin B., Henderson R. D., Furlong S., Mathers S., McCombe P. A., Needham M., Ngo S. T., Nicholson G. A., Pamphlett R., Rowe D. B., Steyn F. J., Williams K. L., Mather K. A., Sachdev P. S., Henders A. K., Wallace L., de Carvalho M., Pinto S., Petri S., Weber M., Rouleau G. A., Silani V., Curtis C. J., Breen G., Glass J. D., Brown R. H., Landers J. E., Shaw C. E., Andersen P. M., Groen E. J. N., van Es M. A., Pasterkamp R. J., Fan D., Garton F. C., McRae A. F., Davey Smith G., Gaunt T. R., Eberle M. A., Mill J., McLaughlin R. L., Hardiman O., Kenna K. P., Wray N. R., Tsai E., Runz H., Franke L., Al-Chalabi A., Van Damme P., van den Berg L. H., and Veldink J. H.

Abstract

In the version of this article initially published, the affiliation for Nazli Başak appeared incorrectly. Nazli Başak is at Koç University, School of Medicine, KUTTAM-NDAL, Istanbul, Turkey, and not Bogazici University. The error has been corrected in the HTML and PDF versions of the article.

Published
2022

20. Integrative genetic analysis illuminates ALS heritability and identifies risk genes

Author

Megat, S., Mora, N., Sanogo, J., Roman, O., Catanese, A., Alami, N.O., Freischmidt, A., Mingaj, X., Calbiac, H. De, Muratet, F., Dirrig-Grosch, S., Dieterle, S., Bakel, N. Van, Muller, K., Sieverding, K., Weishaupt, J., Andersen, P.M., Weber, M., Neuwirth, C., Margelisch, M., Sommacal, A., Eijk, K.R. van, Veldink, J.H., Lautrette, G., Couratier, P., Camuzat, A., Ber, I. Le, Grassano, M., Chio, A., Boeckers, T., Ludolph, A.C., Roselli, F., Yilmazer-Hanke, D., Millecamps, S., Kabashi, E., Storkebaum, E.J.M., Sellier, C., Dupuis, L., Megat, S., Mora, N., Sanogo, J., Roman, O., Catanese, A., Alami, N.O., Freischmidt, A., Mingaj, X., Calbiac, H. De, Muratet, F., Dirrig-Grosch, S., Dieterle, S., Bakel, N. Van, Muller, K., Sieverding, K., Weishaupt, J., Andersen, P.M., Weber, M., Neuwirth, C., Margelisch, M., Sommacal, A., Eijk, K.R. van, Veldink, J.H., Lautrette, G., Couratier, P., Camuzat, A., Ber, I. Le, Grassano, M., Chio, A., Boeckers, T., Ludolph, A.C., Roselli, F., Yilmazer-Hanke, D., Millecamps, S., Kabashi, E., Storkebaum, E.J.M., Sellier, C., and Dupuis, L.

Abstract

Item does not contain fulltext

Published
2023

25. Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Author

van Rheenen, W, van der Spek, R, Bakker, M, van Vugt, J, Hop, P, Zwamborn, R, de Klein, N, Westra, H, Bakker, O, Deelen, P, Shireby, G, Hannon, E, Moisse, M, Baird, D, Restuadi, R, Dolzhenko, E, Dekker, A, Gawor, K, Westeneng, H, Tazelaar, G, van Eijk, K, Kooyman, M, Byrne, R, Doherty, M, Heverin, M, Al Khleifat, A, Iacoangeli, A, Shatunov, A, Ticozzi, N, Cooper-Knock, J, Smith, B, Gromicho, M, Chandran, S, Pal, S, Morrison, K, Shaw, P, Hardy, J, Orrell, R, Sendtner, M, Meyer, T, Basak, N, van der Kooi, A, Ratti, A, Fogh, I, Gellera, C, Lauria, G, Corti, S, Cereda, C, Sproviero, D, D'Alfonso, S, Soraru, G, Siciliano, G, Filosto, M, Padovani, A, Chio, A, Calvo, A, Moglia, C, Brunetti, M, Canosa, A, Grassano, M, Beghi, E, Pupillo, E, Logroscino, G, Nefussy, B, Osmanovic, A, Nordin, A, Lerner, Y, Zabari, M, Gotkine, M, Baloh, R, Bell, S, Vourc'H, P, Corcia, P, Couratier, P, Millecamps, S, Meininger, V, Salachas, F, Mora Pardina, J, Assialioui, A, Rojas-Garcia, R, Dion, P, Ross, J, Ludolph, A, Weishaupt, J, Brenner, D, Freischmidt, A, Bensimon, G, Brice, A, Durr, A, Payan, C, Saker-Delye, S, Wood, N, Topp, S, Rademakers, R, Tittmann, L, Lieb, W, Franke, A, Ripke, S, Braun, A, Kraft, J, Whiteman, D, Olsen, C, Uitterlinden, A, Hofman, A, Rietschel, M, Cichon, S, Nothen, M, Amouyel, P, Traynor, B, Singleton, A, Mitne Neto, M, Cauchi, R, Ophoff, R, Wiedau-Pazos, M, Lomen-Hoerth, C, van Deerlin, V, Grosskreutz, J, Roediger, A, Gaur, N, Jork, A, Barthel, T, Theele, E, Ilse, B, Stubendorff, B, Witte, O, Steinbach, R, Hubner, C, Graff, C, Brylev, L, Fominykh, V, Demeshonok, V, Ataulina, A, Rogelj, B, Koritnik, B, Zidar, J, Ravnik-Glavac, M, Glavac, D, Stevic, Z, Drory, V, Povedano, M, Blair, I, Kiernan, M, Benyamin, B, Henderson, R, Furlong, S, Mathers, S, Mccombe, P, Needham, M, Ngo, S, Nicholson, G, Pamphlett, R, Rowe, D, Steyn, F, Williams, K, Mather, K, Sachdev, P, Henders, A, Wallace, L, de Carvalho, M, Pinto, S, Petri, S, Weber, M, Rouleau, G, Silani, V, Curtis, C, Breen, G, Glass, J, Brown, R, Landers, J, Shaw, C, Andersen, P, Groen, E, van Es, M, Pasterkamp, R, Fan, D, Garton, F, Mcrae, A, Davey Smith, G, Gaunt, T, Eberle, M, Mill, J, Mclaughlin, R, Hardiman, O, Kenna, K, Wray, N, Tsai, E, Runz, H, Franke, L, Al-Chalabi, A, Van Damme, P, van den Berg, L, Veldink, J, Ferrarese, C, van Rheenen W., van der Spek R. A. A., Bakker M. K., van Vugt J. J. F. A., Hop P. J., Zwamborn R. A. J., de Klein N., Westra H. -J., Bakker O. B., Deelen P., Shireby G., Hannon E., Moisse M., Baird D., Restuadi R., Dolzhenko E., Dekker A. M., Gawor K., Westeneng H. -J., Tazelaar G. H. P., van Eijk K. R., Kooyman M., Byrne R. P., Doherty M., Heverin M., Al Khleifat A., Iacoangeli A., Shatunov A., Ticozzi N., Cooper-Knock J., Smith B. N., Gromicho M., Chandran S., Pal S., Morrison K. E., Shaw P. J., Hardy J., Orrell R. W., Sendtner M., Meyer T., Basak N., van der Kooi A. J., Ratti A., Fogh I., Gellera C., Lauria G., Corti S., Cereda C., Sproviero D., D'Alfonso S., Soraru G., Siciliano G., Filosto M., Padovani A., Chio A., Calvo A., Moglia C., Brunetti M., Canosa A., Grassano M., Beghi E., Pupillo E., Logroscino G., Nefussy B., Osmanovic A., Nordin A., Lerner Y., Zabari M., Gotkine M., Baloh R. H., Bell S., Vourc'h P., Corcia P., Couratier P., Millecamps S., Meininger V., Salachas F., Mora Pardina J. S., Assialioui A., Rojas-Garcia R., Dion P. A., Ross J. P., Ludolph A. C., Weishaupt J. H., Brenner D., Freischmidt A., Bensimon G., Brice A., Durr A., Payan C. A. M., Saker-Delye S., Wood N. W., Topp S., Rademakers R., Tittmann L., Lieb W., Franke A., Ripke S., Braun A., Kraft J., Whiteman D. C., Olsen C. M., Uitterlinden A. G., Hofman A., Rietschel M., Cichon S., Nothen M. M., Amouyel P., Traynor B. J., Singleton A. B., Mitne Neto M., Cauchi R. J., Ophoff R. A., Wiedau-Pazos M., Lomen-Hoerth C., van Deerlin V. M., Grosskreutz J., Roediger A., Gaur N., Jork A., Barthel T., Theele E., Ilse B., Stubendorff B., Witte O. W., Steinbach R., Hubner C. A., Graff C., Brylev L., Fominykh V., Demeshonok V., Ataulina A., Rogelj B., Koritnik B., Zidar J., Ravnik-Glavac M., Glavac D., Stevic Z., Drory V., Povedano M., Blair I. P., Kiernan M. C., Benyamin B., Henderson R. D., Furlong S., Mathers S., McCombe P. A., Needham M., Ngo S. T., Nicholson G. A., Pamphlett R., Rowe D. B., Steyn F. J., Williams K. L., Mather K. A., Sachdev P. S., Henders A. K., Wallace L., de Carvalho M., Pinto S., Petri S., Weber M., Rouleau G. A., Silani V., Curtis C. J., Breen G., Glass J. D., Brown R. H., Landers J. E., Shaw C. E., Andersen P. M., Groen E. J. N., van Es M. A., Pasterkamp R. J., Fan D., Garton F. C., McRae A. F., Davey Smith G., Gaunt T. R., Eberle M. A., Mill J., McLaughlin R. L., Hardiman O., Kenna K. P., Wray N. R., Tsai E., Runz H., Franke L., Al-Chalabi A., Van Damme P., van den Berg L. H., Veldink J. H., Ferrarese C., van Rheenen, W, van der Spek, R, Bakker, M, van Vugt, J, Hop, P, Zwamborn, R, de Klein, N, Westra, H, Bakker, O, Deelen, P, Shireby, G, Hannon, E, Moisse, M, Baird, D, Restuadi, R, Dolzhenko, E, Dekker, A, Gawor, K, Westeneng, H, Tazelaar, G, van Eijk, K, Kooyman, M, Byrne, R, Doherty, M, Heverin, M, Al Khleifat, A, Iacoangeli, A, Shatunov, A, Ticozzi, N, Cooper-Knock, J, Smith, B, Gromicho, M, Chandran, S, Pal, S, Morrison, K, Shaw, P, Hardy, J, Orrell, R, Sendtner, M, Meyer, T, Basak, N, van der Kooi, A, Ratti, A, Fogh, I, Gellera, C, Lauria, G, Corti, S, Cereda, C, Sproviero, D, D'Alfonso, S, Soraru, G, Siciliano, G, Filosto, M, Padovani, A, Chio, A, Calvo, A, Moglia, C, Brunetti, M, Canosa, A, Grassano, M, Beghi, E, Pupillo, E, Logroscino, G, Nefussy, B, Osmanovic, A, Nordin, A, Lerner, Y, Zabari, M, Gotkine, M, Baloh, R, Bell, S, Vourc'H, P, Corcia, P, Couratier, P, Millecamps, S, Meininger, V, Salachas, F, Mora Pardina, J, Assialioui, A, Rojas-Garcia, R, Dion, P, Ross, J, Ludolph, A, Weishaupt, J, Brenner, D, Freischmidt, A, Bensimon, G, Brice, A, Durr, A, Payan, C, Saker-Delye, S, Wood, N, Topp, S, Rademakers, R, Tittmann, L, Lieb, W, Franke, A, Ripke, S, Braun, A, Kraft, J, Whiteman, D, Olsen, C, Uitterlinden, A, Hofman, A, Rietschel, M, Cichon, S, Nothen, M, Amouyel, P, Traynor, B, Singleton, A, Mitne Neto, M, Cauchi, R, Ophoff, R, Wiedau-Pazos, M, Lomen-Hoerth, C, van Deerlin, V, Grosskreutz, J, Roediger, A, Gaur, N, Jork, A, Barthel, T, Theele, E, Ilse, B, Stubendorff, B, Witte, O, Steinbach, R, Hubner, C, Graff, C, Brylev, L, Fominykh, V, Demeshonok, V, Ataulina, A, Rogelj, B, Koritnik, B, Zidar, J, Ravnik-Glavac, M, Glavac, D, Stevic, Z, Drory, V, Povedano, M, Blair, I, Kiernan, M, Benyamin, B, Henderson, R, Furlong, S, Mathers, S, Mccombe, P, Needham, M, Ngo, S, Nicholson, G, Pamphlett, R, Rowe, D, Steyn, F, Williams, K, Mather, K, Sachdev, P, Henders, A, Wallace, L, de Carvalho, M, Pinto, S, Petri, S, Weber, M, Rouleau, G, Silani, V, Curtis, C, Breen, G, Glass, J, Brown, R, Landers, J, Shaw, C, Andersen, P, Groen, E, van Es, M, Pasterkamp, R, Fan, D, Garton, F, Mcrae, A, Davey Smith, G, Gaunt, T, Eberle, M, Mill, J, Mclaughlin, R, Hardiman, O, Kenna, K, Wray, N, Tsai, E, Runz, H, Franke, L, Al-Chalabi, A, Van Damme, P, van den Berg, L, Veldink, J, Ferrarese, C, van Rheenen W., van der Spek R. A. A., Bakker M. K., van Vugt J. J. F. A., Hop P. J., Zwamborn R. A. J., de Klein N., Westra H. -J., Bakker O. B., Deelen P., Shireby G., Hannon E., Moisse M., Baird D., Restuadi R., Dolzhenko E., Dekker A. M., Gawor K., Westeneng H. -J., Tazelaar G. H. P., van Eijk K. R., Kooyman M., Byrne R. P., Doherty M., Heverin M., Al Khleifat A., Iacoangeli A., Shatunov A., Ticozzi N., Cooper-Knock J., Smith B. N., Gromicho M., Chandran S., Pal S., Morrison K. E., Shaw P. J., Hardy J., Orrell R. W., Sendtner M., Meyer T., Basak N., van der Kooi A. J., Ratti A., Fogh I., Gellera C., Lauria G., Corti S., Cereda C., Sproviero D., D'Alfonso S., Soraru G., Siciliano G., Filosto M., Padovani A., Chio A., Calvo A., Moglia C., Brunetti M., Canosa A., Grassano M., Beghi E., Pupillo E., Logroscino G., Nefussy B., Osmanovic A., Nordin A., Lerner Y., Zabari M., Gotkine M., Baloh R. H., Bell S., Vourc'h P., Corcia P., Couratier P., Millecamps S., Meininger V., Salachas F., Mora Pardina J. S., Assialioui A., Rojas-Garcia R., Dion P. A., Ross J. P., Ludolph A. C., Weishaupt J. H., Brenner D., Freischmidt A., Bensimon G., Brice A., Durr A., Payan C. A. M., Saker-Delye S., Wood N. W., Topp S., Rademakers R., Tittmann L., Lieb W., Franke A., Ripke S., Braun A., Kraft J., Whiteman D. C., Olsen C. M., Uitterlinden A. G., Hofman A., Rietschel M., Cichon S., Nothen M. M., Amouyel P., Traynor B. J., Singleton A. B., Mitne Neto M., Cauchi R. J., Ophoff R. A., Wiedau-Pazos M., Lomen-Hoerth C., van Deerlin V. M., Grosskreutz J., Roediger A., Gaur N., Jork A., Barthel T., Theele E., Ilse B., Stubendorff B., Witte O. W., Steinbach R., Hubner C. A., Graff C., Brylev L., Fominykh V., Demeshonok V., Ataulina A., Rogelj B., Koritnik B., Zidar J., Ravnik-Glavac M., Glavac D., Stevic Z., Drory V., Povedano M., Blair I. P., Kiernan M. C., Benyamin B., Henderson R. D., Furlong S., Mathers S., McCombe P. A., Needham M., Ngo S. T., Nicholson G. A., Pamphlett R., Rowe D. B., Steyn F. J., Williams K. L., Mather K. A., Sachdev P. S., Henders A. K., Wallace L., de Carvalho M., Pinto S., Petri S., Weber M., Rouleau G. A., Silani V., Curtis C. J., Breen G., Glass J. D., Brown R. H., Landers J. E., Shaw C. E., Andersen P. M., Groen E. J. N., van Es M. A., Pasterkamp R. J., Fan D., Garton F. C., McRae A. F., Davey Smith G., Gaunt T. R., Eberle M. A., Mill J., McLaughlin R. L., Hardiman O., Kenna K. P., Wray N. R., Tsai E., Runz H., Franke L., Al-Chalabi A., Van Damme P., van den Berg L. H., Veldink J. H., and Ferrarese C.

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.

Published
2021

27. Predictive genetic testing for Motor neuron disease: time for a guideline?

Author

McNeill, A, Amador, M-D-M, Bekker, H, Clarke, A, Crook, A, Cummings, C, McEwen, A, McDermott, C, Quarrell, O, Renieri, A, Roggenbuck, J, Salmon, K, Volk, A, Weishaupt, J, and International Alliance of ALS/MND Associations

Subjects
Genetics & Heredity, 0604 Genetics, 1103 Clinical Sciences, Amyotrophic Lateral Sclerosis, Humans, Genetic Testing, Motor Neuron Disease
Published
2022

29. FUS mutations dominate TBK1 mutations in FUS/TBK1 double-mutant ALS/FTD pedigrees

Author

Brenner, D., Muller, K., Lattante, Serena, Yilmaz, R., Knehr, A., Freischmidt, A., Ludolph, A. C., Andersen, P. M., Weishaupt, J. H., Lattante S. (ORCID:0000-0003-2891-0340), Brenner, D., Muller, K., Lattante, Serena, Yilmaz, R., Knehr, A., Freischmidt, A., Ludolph, A. C., Andersen, P. M., Weishaupt, J. H., and Lattante S. (ORCID:0000-0003-2891-0340)

Abstract

Mutations in FUS and TBK1 often cause aggressive early-onset amyotrophic lateral sclerosis (ALS) or a late-onset ALS and/or frontotemporal dementia (FTD) phenotype, respectively. Co-occurrence of mutations in two or more Mendelian ALS/FTD genes has been repeatedly reported. However, little is known how two pathogenic ALS/FTD mutations in the same patient interact to shape the final phenotype. We screened 28 ALS patients with a known FUS mutation by whole-exome sequencing and targeted evaluation for mutations in other known ALS genes followed by genotype–phenotype correlation analysis of FUS/TBK1 double-mutant patients. We report on new and summarize previously published FUS and TBK1 double-mutant ALS/FTD patients and their families. We found that, within a family, mutations in FUS cause ALS while TBK1 single mutations are observed in FTD patients. FUS/TBK1 double mutations manifested as ALS and without a manifest difference regarding age at onset and disease duration when compared to FUS single-mutant individuals. In conclusion, TBK1 and FUS variants do not seem to interact in a simple additive way. Rather, the phenotype of FUS/TBK1 double-mutant patients appears to be dominated by the FUS mutation.

Published
2022

32. Author Correction: Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology (Nature Genetics, (2021), 53, 12, (1636-1648), 10.1038/s41588-021-00973-1)

Author

van Rheenen, W., van der Spek, R. A. A., Bakker, M. K., van Vugt, J. J. F. A., Hop, P. J., Zwamborn, R. A. J., de Klein, N., Westra, H. -J., Bakker, O. B., Deelen, P., Shireby, G., Hannon, E., Moisse, M., Baird, D., Restuadi, R., Dolzhenko, E., Dekker, A. M., Gawor, K., Westeneng, H. -J., Tazelaar, G. H. P., van Eijk, K. R., Kooyman, M., Byrne, R. P., Doherty, M., Heverin, M., Al Khleifat, A., Iacoangeli, A., Shatunov, A., Ticozzi, N., Cooper-Knock, J., Smith, B. N., Gromicho, M., Chandran, S., Pal, S., Morrison, K. E., Shaw, P. J., Hardy, J., Orrell, R. W., Sendtner, M., Meyer, T., Basak, N., van der Kooi, A. J., Ratti, A., Fogh, I., Gellera, C., Lauria, G., Corti, S., Cereda, C., Sproviero, D., D'Alfonso, S., Soraru, G., Siciliano, G., Filosto, M., Padovani, A., Chio, A., Calvo, A., Moglia, C., Brunetti, M., Canosa, A., Grassano, M., Beghi, E., Pupillo, E., Logroscino, G., Nefussy, B., Osmanovic, A., Nordin, A., Lerner, Y., Zabari, M., Gotkine, M., Baloh, R. H., Bell, S., Vourc'H, P., Corcia, P., Couratier, P., Millecamps, S., Meininger, V., Salachas, F., Mora Pardina, J. S., Assialioui, A., Rojas-Garcia, R., Dion, P. A., Ross, J. P., Ludolph, A. C., Weishaupt, J. H., Brenner, D., Freischmidt, A., Bensimon, G., Brice, A., Durr, A., Payan, C. A. M., Saker-Delye, S., Wood, N. W., Topp, S., Rademakers, R., Tittmann, L., Lieb, W., Franke, A., Ripke, S., Braun, A., Kraft, J., Whiteman, D. C., Olsen, C. M., Uitterlinden, A. G., Hofman, A., Rietschel, M., Cichon, S., Nothen, M. M., Amouyel, P., Comi, G., Riva, N., Lunetta, C., Gerardi, F., Cotelli, M. S., Rinaldi, F., Chiveri, L., Guaita, M. C., Perrone, P., Ceroni, M., Diamanti, L., Ferrarese, C., Tremolizzo, L., Delodovici, M. L., Bono, G., Manera, U., Vasta, R., Bombaci, A., Casale, F., Fuda, G., Salamone, P., Iazzolino, B., Peotta, L., Cugnasco, P., De Marco, G., Torrieri, M. C., Palumbo, F., Gallone, S., Barberis, M., Sbaiz, L., Gentile, S., Mauro, A., Mazzini, L., De Marchi, F., Corrado, L., Bertolotto, A., Gionco, M., Leotta, D., Odddenino, E., Imperiale, D., Cavallo, R., Pignatta, P., De Mattei, M., Geda, C., Papurello, D. M., Gusmaroli, G., Comi, C., Labate, C., Ruiz, L., Ferrandi, D., Rota, E., Aguggia, M., Di Vito, N., Meineri, P., Ghiglione, P., Launaro, N., Dotta, M., Di Sapio, A., Giardini, G., Tiloca, C., Peverelli, S., Taroni, F., Pensato, V., Castellotti, B., Comi, G. P., Del Bo, R., Gagliardi, S., Raggi, F., Simoncini, C., Lo Gerfo, A., Inghilleri, M., Ferlini, A., Simone, I. L., Passarella, B., Guerra, V., Zoccolella, S., Nozzoli, C., Mundi, C., Leone, M., Zarrelli, M., Tamma, F., Valluzzi, F., Calabrese, G., Boero, G., Rini, A., Traynor, B. J., Singleton, A. B., Mitne Neto, M., Cauchi, R. J., Ophoff, R. A., Wiedau-Pazos, M., Lomen-Hoerth, C., van Deerlin, V. M., Grosskreutz, J., Roediger, A., Gaur, N., Jork, A., Barthel, T., Theele, E., Ilse, B., Stubendorff, B., Witte, O. W., Steinbach, R., Hubner, C. A., Graff, C., Brylev, L., Fominykh, V., Demeshonok, V., Ataulina, A., Rogelj, B., Koritnik, B., Zidar, J., Ravnik-Glavac, M., Glavac, D., Stevic, Z., Drory, V., Povedano, M., Blair, I. P., Kiernan, M. C., Benyamin, B., Henderson, R. D., Furlong, S., Mathers, S., Mccombe, P. A., Needham, M., Ngo, S. T., Nicholson, G. A., Pamphlett, R., Rowe, D. B., Steyn, F. J., Williams, K. L., Mather, K. A., Sachdev, P. S., Henders, A. K., Wallace, L., de Carvalho, M., Pinto, S., Petri, S., Weber, M., Rouleau, G. A., Silani, V., Curtis, C. J., Breen, G., Glass, J. D., Brown, R. H., Landers, J. E., Shaw, C. E., Andersen, P. M., Groen, E. J. N., van Es, M. A., Pasterkamp, R. J., Fan, D., Garton, F. C., Mcrae, A. F., Davey Smith, G., Gaunt, T. R., Eberle, M. A., Mill, J., Mclaughlin, R. L., Hardiman, O., Kenna, K. P., Wray, N. R., Tsai, E., Runz, H., Franke, L., Al-Chalabi, A., Van Damme, P., van den Berg, L. H., and Veldink, J. H.

Published
2022

35. The European Employment Strategy: assessing the status quo

Author

Weishaupt, J. Timo and Lack, Katja

Subjects
Employment, Government, International relations, Political science, Regional focus/area studies, European Union. Council of the European Union -- Training -- Employment, European Union. European Commission -- Training -- Employment
Abstract

The European Employment Strategy (EES) is the European Union's main instrument to co-ordinate Member States' reform efforts in the area of labour market and social policies. Launched in 1997, it has undergone various changes, both in its governance and its policy orientation. This paper offers an overview of the EES's origins, main functions and evolution. It also critically reflects on its development and closes with a succinct presentation and assessment of the EES in the context of the Europe 2020 Strategy that has replaced the expired Lisbon Strategy., 1 Introduction (1) When it comes to employment-related issues, 2010 was a critical year for Europe in at least two ways. First, following the 'Great Recession' of 2009, only few [...]

Published
2011

43. Necrosome‐positive granulovacuolar degeneration is associated with TDP‐43 pathological lesions in the hippocampus of ALS/FTLD cases

Author

Van Schoor, E., primary, Koper, M. J., additional, Ospitalieri, S., additional, Dedeene, L., additional, Tomé, S. O., additional, Vandenberghe, R., additional, Brenner, D., additional, Otto, M., additional, Weishaupt, J., additional, Ludolph, A. C., additional, Van Damme, P., additional, Van Den Bosch, L., additional, and Thal, D. R., additional

Published
2020
Full Text
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49. Rare heterozygous DHTKD1 variants in patients with amyotrophic lateral sclerosis

Author

Gogol, I., Osmanovic, A., Martens, H., Widjaja, M., Mueller, K., Schreiber-Katz, O., Schmidt, G., Auber, B., Andersen, Peter M., Ludolph, A., Weishaupt, J., Brand, F., Petri, S., Weber, R. G., Gogol, I., Osmanovic, A., Martens, H., Widjaja, M., Mueller, K., Schreiber-Katz, O., Schmidt, G., Auber, B., Andersen, Peter M., Ludolph, A., Weishaupt, J., Brand, F., Petri, S., and Weber, R. G.

Abstract

Supplement: 1Meeting Abstract: P10.15.A

Published
2020

50. ROCK-ALS: Protocol for a Randomized, Placebo-Controlled, Double-Blind Phase IIa Trial of Safety, Tolerability and Efficacy of the Rho Kinase (ROCK) Inhibitor Fasudil in Amyotrophic Lateral Sclerosis

Author

Lingor, Paul, Weber, Markus, Bidner, Helen, Blankenstein, Christiane, Frontini, Roberto, Ludolph, Albert, Koch, Jan C, Investigators, ROCK-ALS, Attarian, Shahram, Bähr, Mathias, Boentert, Matthias, Braun, Nathalie, Camu, William, Corcia, Philippe, Cordts, Isabell, Deschauer, Marcus, Grehl, Thorsten, Grosskreutz, Julian, Hermann, Andreas, Kuttler, Josua, Lengenfeldt, Teresa, Maass, Fabian, Meyer, Thomas, Friede, Tim, Petri, Susanne, Remane, Yvonne, Schmidt, Jens, Schuster, Joachim, Soriani, Marie-Hélène, Statland, Jeffrey, Weishaupt, J, Zeller, Daniel, Zielke, Eirini, Hilgers, Reinhard, Leha, Andreas, Neuwirth, Christoph, Günther, René, Benatar, Michael, and Kuzma-Kozakiewicz, Magdalena

Subjects
clinical trial protocol, amyotrophic lateral sclerosis, study design, Neurology, ROCK inhibition, disease-modification, Clinical Study Protocol, ddc:610
Abstract

Objectives: Disease-modifying therapies for amyotrophic lateral sclerosis (ALS) are still not satisfactory. The Rho kinase (ROCK) inhibitor fasudil has demonstrated beneficial effects in cell culture and animal models of ALS. For many years, fasudil has been approved in Japan for the treatment of vasospasm in patients with subarachnoid hemorrhage with a favorable safety profile. Here we describe a clinical trial protocol to repurpose fasudil as a disease-modifying therapy for ALS patients. Methods: ROCK-ALS is a multicenter, double-blind, randomized, placebo-controlled phase IIa trial of fasudil in ALS patients (EudraCT: 2017-003676-31, NCT: 03792490). Safety and tolerability are the primary endpoints. Efficacy is a secondary endpoint and will be assessed by the change in ALSFRS-R, ALSAQ-5, slow vital capacity (SVC), ECAS, and the motor unit number index (MUNIX), as well as survival. Efficacy measures will be assessed before (baseline) and immediately after the infusion therapy as well as on days 90 and 180. Patients will receive a daily dose of either 30 or 60 mg fasudil, or placebo in two intravenous applications for a total of 20 days. Regular assessments of safety will be performed throughout the treatment period, and in the follow-up period until day 180. Additionally, we will collect biological fluids to assess target engagement and evaluate potential biomarkers for disease progression. A total of 120 patients with probable or definite ALS (revised El Escorial criteria) and within 6-18 months of the onset of weakness shall be included in 16 centers in Germany, Switzerland and France. Results and conclusions: The ROCK-ALS trial is a phase IIa trial to evaluate the ROCK-inhibitor fasudil in early-stage ALS-patients that started patient recruitment in 2019. Open-Access-Publikationsfonds 2019 peerReviewed

Published
2019
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