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87 results on '"Panzara, M. A."'

1. P22 WVE-N531 yields 53% mean exon 53 skipping in skeletal muscle of boys with Duchenne muscular dystrophy (DMD) after three biweekly doses

Author

Tillinger, M., primary, Lake, S., additional, Servais, L., additional, Campbell, C., additional, Xu, X., additional, Hart, A., additional, Haegele, J., additional, Singh, K., additional, Rheinhardt, J., additional, Ghosh, A., additional, Xu, D., additional, Panzara, M., additional, and Li-Kwai-Cheung, A., additional

Published
2023
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3. FP.12 Application for primary endpoint qualification of the 95th centile of stride velocity (SV95C) in Duchenne muscular dystrophy

Author

Annoussamy, M., primary, Eggenspieler, D., additional, Seferian, A., additional, Mercuri, E., additional, Straub, V., additional, Muntoni, F., additional, Scoto, M., additional, Poleur, M., additional, Daron, A., additional, Butoianu, N., additional, Mirea, A., additional, Goemans, N., additional, Previtali, S., additional, Tulinius, M., additional, Nascimento, A., additional, Heydemann, P., additional, Panzara, M., additional, Singh, T., additional, Strijbos, P., additional, and Servais, L., additional

Published
2022
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4. The efficacy of natalizumab in patients with relapsing multiple sclerosis: subgroup analyses of AFFIRM and SENTINEL

Author

Hutchinson, M., Kappos, L., Calabresi, P. A., Confavreux, C., Giovannoni, G., Galetta, S. L., Havrdova, E., Lublin, F. D., Miller, D. H., O’Connor, P. W., Phillips, J. T., Polman, C. H., Radue, E.-W., Rudick, R. A., Stuart, W. H., Wajgt, A., Weinstock-Guttman, B., Wynn, D. R., Lynn, F., Panzara, M. A., and for the AFFIRM and SENTINEL Investigators

Published
2009
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8. EP.83Design of a Phase 2/3 randomized controlled trial of suvodirsen (WVE-210201) in patients with Duchenne muscular dystrophy amenable to exon 51 skipping

Author

Wagner, K., primary, Cripe, L., additional, Eagle, M., additional, Muntoni, F., additional, Niks, E., additional, Phan, H., additional, Straub, V., additional, Hu, X., additional, Antonijevic, I., additional, Berry, S., additional, Quintana, M., additional, Lake, S., additional, and Panzara, M., additional

Published
2019
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9. The MSOAC approach to developing performance outcomes to measure and monitor multiple sclerosis disability

Author

LaRocca, NG, Hudson, LD, Rudick, R, Amtmann, D, Balcer, L, Benedict, R, Bermel, R, Chang, I, Chiaravalloti, ND, Chin, P, Cohen, JA, Cutter, GR, Davis, MD, DeLuca, J, Feys, P, Francis, G, Goldman, MD, Hartley, E, Kapoor, R, Lublin, F, Lundstrom, G, Matthews, PM, Mayo, N, Meibach, R, Miller, DM, Motl, RW, Mowry, EM, Naismith, R, Neville, J, Panagoulias, J, Panzara, M, Phillips, G, Robbins, A, Sidovar, MF, Smith, KE, Sperling, B, Uitdehaag, BM, Weaver, J, Multiple Sclerosis Outcome Assessments Consortium (MSOAC), Neurology, Amsterdam Neuroscience - Neuroinfection & -inflammation, and Medical Research Council (MRC)

Subjects
STATUS SCALE, medicine.medical_specialty, Multiple Sclerosis, Databases, Factual, IMPACT, Clinical Neurology, CONTRAST LETTER ACUITY, Measure (physics), Disability Evaluation, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Outcome Assessment, Health Care, medicine, EMPLOYMENT, Humans, MS disability, performance outcome measures, data standards, clinical trial database, regulatory qualification, 030212 general & internal medicine, VALIDITY, SPEED, Functional composite, PROGRESSIVE MS, Science & Technology, Neurology & Neurosurgery, business.industry, Multiple sclerosis, Neurosciences, FUNCTIONAL COMPOSITE, 1103 Clinical Sciences, IMPAIRMENT, medicine.disease, Multiple Sclerosis Outcome Assessments Consortium (MSOAC), Clinical neurology, Neurology, Physical therapy, Neurosciences & Neurology, HEALTH, Neurology (clinical), 1109 Neurosciences, business, Life Sciences & Biomedicine, Original Research Papers, 030217 neurology & neurosurgery
Abstract

Background: The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) was formed by the National MS Society to develop improved measures of multiple sclerosis (MS)-related disability. Objectives: (1) To assess the current literature and available data on functional performance outcome measures (PerfOs) and (2) to determine suitability of using PerfOs to quantify MS disability in MS clinical trials. Methods: (1) Identify disability dimensions common in MS; (2) conduct a comprehensive literature review of measures for those dimensions; (3) develop an MS Clinical Data Interchange Standards Consortium (CDISC) data standard; (4) create a database of standardized, pooled clinical trial data; (5) analyze the pooled data to assess psychometric properties of candidate measures; and (6) work with regulatory agencies to use the measures as primary or secondary outcomes in MS clinical trials. Conclusion: Considerable data exist supporting measures of the functional domains ambulation, manual dexterity, vision, and cognition. A CDISC standard for MS (http://www.cdisc.org/therapeutic#MS) was published, allowing pooling of clinical trial data. MSOAC member organizations contributed clinical data from 16 trials, including 14,370 subjects. Data from placebo-arm subjects are available to qualified researchers. This integrated, standardized dataset is being analyzed to support qualification of disability endpoints by regulatory agencies. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: MSOAC is funded largely through the National Multiple Sclerosis Society grant (no. RG 4869-A-1) to the Critical Path Institute. Annual dues from sponsors supplement the NMSS grant.

Published
2018
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11. Preclinical studies of WVE-210201, an investigational stereopure antisense oligonucleotide in development for the treatment of patients with duchenne muscular dystrophy (DMD)

Author

Panzara, M., primary, Zhang, J., additional, Rinaldi, C., additional, McClorey, G., additional, Bowman, K., additional, Butler, D., additional, Dodart, J., additional, Frank-Kamenetsky, M., additional, Iwamoto, N., additional, Kothari, N., additional, Lu, G., additional, Mathieu, S., additional, M, M., additional, Melkonian, M., additional, Menon, S., additional, Standley, S., additional, Yang, H., additional, Zhong, Z., additional, Wood, M., additional, and Vargeese, C., additional

Published
2017
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12. Health-related quality of life in multiple sclerosis: Effects of natalizumab

Author

Rudick, R. A., Miller, D., Hass, S., Hutchinson, M, Calabresi, P. A., Confavreux, C., Galetta, S. L., Giovannoni, G., Havrdova, E., Kappos, L., Lublin, F. D., Miller, D. H., O'Connor, P. W., Phillips, J. T., Polman, C. H., Radue, Ew, Stuart, W. H., Wajgt, A., Weinstock Guttman, B., Wynn, D. R., Lynn, F., Panzara, M. A., Affirm, Macdonell, SENTINEL Investigators including: R., Hughes, A., Taylor, I., Lee, Y. C., Ma, H., King, J., Kilpatrick, T., Butzkueven, H., Marriott, M., Pollard, J., Spring, P., Spies, J., Barnett, M., Dehaene, I., Vanopdenbosch, L., D’Hooghe, M., Van Zandijcke, M., Derijck, O., Seeldrayers, P., Jacquy, J., Piette, T., De Cock, C., Medaer, R., Soors, P., Vanroose, E., Vanderhoven, L., Nagels, G., Dubois, B., Deville, M. C., D’Haene, R., Jacques, F., Hallé, D., Gagnon, S., Likavcan, E., Murray, T. J., Bhan, V., Mackelvey, R., Maxner, C. E., Christie, S., Giaccone, R., Guzman, D. A., Melanson, M., Esfahani, F., Gomori, A. J., Nagaria, M. H., Grand’Maison, F., Berger, L., Nasreddine, Z., Duplessis, M., Brunet, D., Jackson, A., Pari, G., O’Connor, P., Gray, T., Hohol, M., Marchetti, P., Lee, L., Murray, B., Sahlas, J., Perry, J., Devonshire, V., Hooge, J., Hashimoto, S., Oger, J., Smyth, P., Rice, G., Kremenchutzky, M., Stourac, P., Kadanka, Z., Benesova, Y., Niedermayerova, I., Meluzinova, E., Marusic, P., M, Bojar, Zarubova, K., Houzvicková, E., Piková, J., Talab, R., Faculty, Hospital Olomouc, Olomouc, B. Muchova, Urbánek, K, Kettnerova, Z., Mares, J., Otruba, P., Zapletalová, O., Hradilek, P., Ddolezil, D. Dolezil, Woznicova, I., Höfer, R., Ambler J. Fiedler, Z. Ambler J. Fiedler, Sucha, J., Matousek, V., Rektor, I., Dufek, M., Mikulik, R., Mastik, J., Tyrlikova, I., General, Teaching Hospital, Prague, E. Havrdová, Horakova, D., Kalistová, H., Týblová, M., Ehler, E., Novotná, A., Geier, P., Soelberg Sorensen, P., Ravnborg, M., Petersen, B., Blinkenberg, M., Färkkilä, M., Harno, H., Kallela, M., Häppölä, O., Elovaara, I., Kuusisto, H., Ukkonen, M., Peltola, J., Palmio, J., Pelletier, J., Feuillet, L., Suchet, L., Dalecky, A., Tammam, D., Edan, G., Le Page, E., Mérienne, M., Yaouanq, J., Clanet, M., Mekies, C., Azais Vuillemin, C., Senard, A., Lau, G., Steinmetz, G., Warter V. Wolff, J. Warter V. Wolff, Fleury, M., Tranchant, C., Stark, E., Buckpesch Heberer, U., Henn, K. H., Skoberne, T., Schimrigk, S., Hellwig, K., Brune, N., Weiller, C., Gbadamosi, J., Röther, J., Heesen, C., Buhmann, C., Karageorgiou, C., Korakaki, D., Giannoulis, D. r., Tsiara, S., Thomaides, T., Thomopoulos, I., Papageorgiou, H., Armakola, F., Komoly, S., Rózsa, C., Matolcsi, J., Szabó, G. y., Molnár, B., Lovas, G., Dioszeghy, P., Szulics, P., Magyar, Z., Incze, J., Farkas, J., Clemens, B., Kánya, J., Valicskó, Z. s., Bense, E., Nagy, Z. s., Geréby, G., Perényi, J., Simon, Z. s., Szapper, M., Gedeon, L., Csanyi, A., Rum, G., Lipóth, S., Szegedi, A., Jávor, L., Nagy, I., Adám, I., Szirmai, I., Simó, M., Ertsey, C., I, Amrein, Kamondi, A., Harcos, P., Dobos, E., Szabó, B., Balas, V., Guseo, A., Fodor, E., Jófejü, E., Eizler, K., Csiba, L., Csépány, T., Pallagi, E., Bereczki, D., Jakab, G., Juhász, M., Bszabó, B. Szabó I. Mayer, Katona, G., Hutchinson, M., O’Dwyer, J., O’Rourke, K., Sanders, E. A. C. M., Rijk van Andel, J. F., Bomhof, M. A. M., van Erven, P., Hintzen I. Hoppenbrouwers, R. Q. Hintzen I. Hoppenbrouwers, Neuteboom, R. F., Zemel, D., van Doorn, P. A., Jacobs, B. C., Munster, E. T. h. L. Van, ter Bruggen, J. P., Bernsen, R., Jongen, P. J. H., de Smet, E. A. A., Tacken, H. F. H., Polman, C., Zwemmer, J., Nielsen, J., Kalkers, N., Kragt, J., Jasperse, B., Willoughby, E., Anderson, N. E., Barber, A., Anderson, T., Parkin, P. J., Fink, J., Avery, S., Mason, D., Kwiecinski, H., Zakrzewska Pniewska, B., Kaminska, A., Podlecka, A., Nojszewska, M., Czlonkowska, A., Zaborski, J., Wicha, W., Kruszewska Ozimowska, J., Darda Ledzion, L., Selmaj, K., Mochecka Thoelke, A., Pentela Nowicka, J., Walczak, A., Stasiolek, M., Stelmasiak, Z., Bartosik Psujek, H., Mitosek Szewczyk, K., Belniak, E., Chyrchel, U., Maciejowski, M., Strzyzewska Lubos, L., Lubos, L., Matusik, E., Maciejek, Z., Niezgodzinska Maciejek, A., Sobczynska, D., Slotala, T., Wawrzyniak, S., Kochanowicz K. Kuczynski, J. Kochanowicz K. Kuczynski, Zimnoch, R., Pryszmont, M., Drozdowski, W., Baniukiewicz, E., Kulakowska, A., Borowik, H., Lewonowska, M., Szczudlik, A., Róg, T., Gryz Kurek, E., Pankiewicz, J., Furgal, J., Kimkowicz, A., Fryze, W., Wierbicki, T., Michalak, L., Kowalewska, J., Swiatkiewicz, J., Hillert, J., Åkesson, E, Fredrikson, S., Diener, P, Olsson, T., Wallström, E., Fpiehl, F. Piehl L. Hopia, Brundin, L., Marta, M., Andersson, M., Lycke, J., Runmarker, B., Malmeström, C., Vaghfeldt, P., Skoog, B., Schluep, M., Bogousslavskyr, J., Du Pasquier, R., Achtnichts, L., Kuhle, J., Buitrago Telez, C., Schläger, R., Naegelin, Y., Eraksoy, M., Bebek, N., Akman Demir, G., Topcuoglu, B., Kurtuncu, M., Istanbul, University, Istanbul:, A. Siva, Saip, S., Altintas, A., Kiyat, A., Sharief, M., Kasti, M., Lim, E. T., Rashid, W., Silber, E., Saldanha, G., Hawkins, C., Mamutse, G., Woolmore, J., Hawkes, C., Findley, L., Dasilva, R., Gunasekara, H., Palace, J., Cader, Z., Littleton, E., Burke, G., Sharrack O. Suliman, B. Sharrack O. Suliman, Klaffke, S., Swash, M., Dhillon, H., Bates, D., Westwood, M., Nichol, P., Barnes, D., Wren, D., Stoy, N., Robertson, N., Pickersgill, T., Pearson, O., Lawthom, C., Young, C., Mills, R., Lecky, B., Ford, C., Katzman, J., Rosenberg, G., Cooper, J., Wrubel, B., Richardson, B., Lynch, S., Ridings, L., Mcvey, A., Nowack, W., Rae Grant, A., Mackin, G. A., Castaldo, J. E., Spikol, L. J., Carter, J., Wingerchuk, D., Caselli, R., Dodick, D., Scarberry, S., Bailly, R., Garnaas, K., Haake, B., Rossman, H., Belkin, M., Boudouris, W. D., Pierce, R. P., Mass, M., Yadav, V., Bourdette, D., Whitham, R. H., Heitzman, D., Martin, A., Greenfield, C. F., Agius, M., Richman, D. P., Vijayan, N., Wheelock, V. L., Reder, A., Arnason, B., Noronha, A., Balabanov, R., Ray, A., Sheremata, W., Delgado, S., Shebert, B., Maldonado, J., Bowen, J., Garden, G. A., Distad, B. J., Carrithers, M., Rizzo, M., Vollmer, T., Reiningerova, J., Guarnaccia, J., Lo, A., Richardson, G. B., Fazekas, F., Enzinger, C., Seifert, T., Storch, M., Strasser Fuchs, S., Berger, T., Dilitz, E., Egg, R., Deisenhammer, F., Decoo, : D, Lampaert, J., Bartholome, E., Bier, J., Stenager, : E., Rasmussen, M., Binzer, M., Shorsh, K., Christensen, M., Soelberg Sørensen, P., Hansen, H. J., Bech, E., Petersen, T., Kirkegaard, M., Eralinna, : J., Ruutiainen, J., Soilu Hänninen, M., Säkö, E., Laaksonen, M., Reunanen, M., Remes, A., Keskinarkaus, I., Moreau, : T., Noblet, M., Rouaud, O., Couvreur, G., Lepage, E., Drapier, S., De Burghgraeve, V., Merienne, M., Cahagne, V., Gout, O., Deschamps, R., Le Canuet, P., Moulignier, A., Vermersch, P., De Seze, J., Stojkovic, T., Griffié, G., Engles, Ferriby, D., Debouverie, M., Pittion Vouyouvitch, S., Lacour, J. C., Lubetzki, C., Youssov, K., Mrejen, S., Charles, P., Yaici, S., Clavelou, P., Aufauvre, D., Renouil Guy, N., Cesaro, P., Degos, F., Benisty, S., Rumbach, L., Decavel, P., Blanc, S., Aubertin, P., Riche, G., Brochet, B., Ouallet, J. C., Anne, O., Menck, : S., Grupe, A., Gutmann, E., Lensch, E., Fucik, E., Heitmann, S., Hartung, H. P., Schröter, M., Kurz, F. M. W., Heidenreich, F., Trebst, C., Pul, R., Hohlfeld, R., Krumbholz, M., Pellkofer, H., Haas, J., Segert, A., Meyer, R., Anagnostou, P., Kabus, C., Poehlau, D., Schneider, K., Hoffmann, V., Zettl, U., Steinhagen, V., Adler, S., Steinbrecher E. Rothenfusser Körber, A. Steinbrecher E. Rothenfusser Körber, Zellner, R., Baum, K., Günther, A., Bläsing, H., Stoll, G., Gold, R., Bayas, A., Kleinschnitz, C., Limmroth, V., Katsarava, Z., Kastrup, O., Haller, P., Stoeve, S., Höbel, D., Oschmann, P., Voigt, K., Burger, C. V., Abramsky, : O., Karusiss, D., Achiron, A., Kishner, I., Stern, Y., Sarove Pinhas, I., Dolev, M., Magalashvili, D., Pozzili, : C., Lenzi, D., Scontrini, A., Millefiorini, E., Buttinelli, C., Gallo, P., Ranzato, F., Tiberio, M., Perini, P., Laroni, Alice, Marrosu, M., Cocco P. Marchi, E. Cocco P. Marchi, Spinicci, G., Massole, S., Mascia, M., Floris, G., Trojano, M., Bellacosa, A., Paolicelli, D., Bosco Zimatore, G., Simone, I. L., Giorelli, M., Di Monte, E., Mancardi, GIOVANNI LUIGI, Pizzorno, M., Murialdo, A., Narciso, E., Capello, A., Comi, G., Martinelli, V., Rodegher, M., Esposito, F., Colombo, B., Rossi, P., Polman, : C. H., Jasperse, M. M. S., Zwemmer, J. N. P., Kragt, J. J., De Smet, E., Tacken, H., Frequin, S. T. F. M., Siegers, H. P., Mauser, H. W., Fernandez Fernandez, : O., León, A., Romero, F., Alonso, A., Tamayo, J., Montalban, X., Nos, C., Pelayo, R., Tellez, N., Rio, J., Tintore, M., Arbizu, T., Romero, L., Moral, E., Martinez, S., Kappos, : L., Wilmes, S., Karabudak, : R., Kurne, A., Erdem, S., Siva, A., Atamer, A., Bilgili, F., Topcular, B., Giovannoni, : G., Lava, : N., Murnane, M., Dentinger, M., Zimmerman, E., Reiss, M., Gupta, V., Scott, T., Brillman, J., Kunschner, L., Wright, D., Perel, A., Babu, A., Rivera, V., Killian, J., Hutton, G., Lai, E., Picone, M., Cadivid, D., Kamin, S., Shanawani, M., Gauthier, S., Morgan, A., Buckle, G., Margolin, D., Kwen, P. L., Garg, N., Munschauer, F., Khatri, B., Rassouli, M., Saxena, V., Ahmed, A., Turner, A., Fox, E., Couch, C., Tyler, R., Horvit, A., Fodor, P., Humphries, S., Wynn, D., Nagar, C., O’Brien, D., Allen, N., Turel, A., Friedenberg, S., Carlson, J., Hosey, J., Crayton, H., Richert, J., Tornatore, C., Sirdofsky, M., Greenstein, J., Shpigel, Y., Mandel, S., Adbelhak, T., Schmerler, M., Zadikoff, C., Rorick, M., Reed, R., Elias, S., Feit, H., Angus, E., Sripathi, N., Herbert, J., Kiprovski, K., Qu, X., Del Bene, M., Mattson, D., Hingtgen, C., Fleck, J., Horak, H., Javerbaum, J., Elmore, R., Garcia, E., Tasch, E., Gruener, G., Celesia, G., Chawla, J., Miller, A., Drexler, E., Keilson, M., Wolintz, R., Drasby, E., Muscat, P., Belden, J., Sullivan, R., Cohen, J., Stone, L., Marrie, R. A., Fox, R., Hughes, B., Babikian, P., Jacoby, M., Doro, J., Puricelli, M., Boudoris, W., Pierce, R., Eggenberger, E., Birbeck, G., Martin, J., Kaufman, D., Stuart, W., English, J. B., Stuart, D. S., Gilbert, R. W., Kaufman, M., Putman, S., Diedrich, A., Follmer, R., Pelletier, D., Waubant, E., Cree, B., Genain, C., Goodin, D., Patwa, H., Rizo, M., Kitaj, M., Blevins, J., Smith, T., Mcgee, F., Honeycutt, W., Brown, M., Isa, A., Nieves Quinones, D., Krupp, L., Smiroldo, J., Zarif, M., Perkins, C., Sumner, A., Fisher, A., Gutierrez, A., Jacoby, R., Svoboda, S., Dorn, D., Groeschel, A., Steingo, B., Kishner, R., Cohen, B., Melen, O., Simuni, T., Zee, P., Cohan, S., Yerby, M., Hendin, B., Levine, T., Tamm, H., Travis, L. H., Freedman, S. M., Tim, R., Ferrell, W., Stefoski, D., Stevens, S., Katsamakis, G., Topel, J., Ko, M., Gelber, D., Fortin, C., Green, B., Logan, W., Carpenter, D., Temple, L., Sadiq, S., Sylvester, A., Sim, G., Mihai, C., Vertino, M., Jubelt, B., Mejico, L., Riskind, P., Cabo, A., Paskavitz, J., Moonis, M., Bashir J. Brockington, K. Bashir J. Brockington, Nicholas, A., Slaughter, R., Archer S. Harik, R. Archer S. Harik, Haddad, N., Pippenger, M. A., Van den Noort, S., Thai, G., Olek, M., Demetriou, M., Shin, R., Calabresi, P., Rus, H., Bever, C., Johnson, K., Sherbert, R., Herndon, R., Uschmann, H., Chandler, A., Markowitz, C., Jacobs, D., Balcer, L., Mitchell, G., Chakravorty, S., Heyman, R., Stauber, Z., Goodman, A., Segal, B., Schwid, S., Samkoff, L., Levin, M., Jacewicz, M., Menkes, D., Pulsinelli, W., Frohman, E., Racke, M., Hawker, K., Ulrich, R., Panitch, H., Hamill, R., Tandon, R., Dulaney, E., Simnad, V., Miller, J., Wooten, G. F., Harrison, M., Doherty, M., Wundes, A., Distad, J., Kachuck, N., Berkovich, R., Burnett, M., Sahai, S., Bandari, D., Weiner, L., Storey, J. R., Beesley, B., Hart, D., Moses, H., Sriram, S., Fang, J., O’Duffy, A., Kita, M., Taylor, L., Elliott, M., Roberts, J., Jeffery, D., Maxwell, S., Lefkowitz, D., Kumar, S., Sinclair, M., Radue, E. W., de Vera, A., Bacelar, O., and Kuster, P.

Subjects
Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Visual analogue scale, Health Status, Population, Pain, Comorbidity, Placebo, Antibodies, law.invention, Natalizumab, Randomized controlled trial, Quality of life, Double-Blind Method, law, Internal medicine, Surveys and Questionnaires, Monoclonal, medicine, Prevalence, Humans, Longitudinal Studies, education, Humanized, education.field_of_study, Expanded Disability Status Scale, Neuroscience (all), business.industry, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Female, Patient Satisfaction, Treatment Outcome, United States, Quality of Life, Multiple sclerosis, medicine.disease, Neurology, Physical therapy, Neurology (clinical), business, medicine.drug
Abstract

Objective To report the relationship between disease activity and health-related quality of life (HRQoL) in relapsing multiple sclerosis, and the impact of natalizumab. Methods HRQoL data were available from 2,113 multiple sclerosis patients in natalizumab clinical studies. In the Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis (AFFIRM) study, patients received natalizumab 300mg (n = 627) or placebo (n = 315); in the Safety and Efficacy of Natalizumab in Combination with Interferon Beta-1a in Patients with Relapsing Remitting Multiple Sclerosis (SENTINEL) study, patients received interferon beta-1a (IFN-β-1a) plus natalizumab 300mg (n = 589), or IFN-β-1a plus placebo (n = 582). The Short Form-36 (SF-36) and a subject global assessment visual analog scale were administered at baseline and weeks 24, 52, and 104. Prespecified analyses included changes from baseline to week 104 in SF-36 and visual analog scale scores. Odds ratios for clinically meaningful improvement or worsening on the SF-36 Physical Component Summary (PCS) and Mental Component Summary were calculated. Results Mean baseline SF-36 scores were significantly less than the general US population and correlated with Expanded Disability Status Scale scores, sustained disability progression, relapse number, and increased volume of brain magnetic resonance imaging lesions. Natalizumab significantly improved SF-36 PCS and Mental Component Summary scores at week 104 in AFFIRM. PCS changes were significantly improved by week 24 and at all subsequent time points. Natalizumab-treated patients in both studies were more likely to experience clinically important improvement and less likely to experience clinically important deterioration on the SF-36 PCS. The visual analog scale also showed significantly improved HRQoL with natalizumab. Interpretation HRQoL was impaired in relapsing multiple sclerosis patients, correlated with severity of disease as measured by neurological ratings or magnetic resonance imaging, and improved significantly with natalizumab. Ann Neurol 2007

Published
2007

14. Adverse event profile of alemtuzumab over time in treatment-naïve patients with early, active relapsing–/INS;remitting multiple sclerosis (RRMS; CARE-MS I study)

Author

Lycke, J., primary, Arnold, D.L., additional, Cohen, J.A., additional, Coles, A.J., additional, Confavreux, C., additional, Fox, E.J., additional, Hartung, H.-P., additional, Havrdova, E., additional, Selmaj, K.W., additional, Weiner, H.L., additional, Brinar, V., additional, Giovannoni, G., additional, Stojanovic, M., additional, Lake, S.L., additional, Margolin, D.H., additional, Panzara, M., additional, and Compston, D.A.S., additional

Published
2013
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15. Alemtuzumab improves visual outcomes in treatment-naïve patients with relapsing–/INS;remitting multiple sclerosis (RRMS): Analysis from the phase 3 CARE-MS I study

Author

Balcer, L.J., primary, Arnold, D.L., additional, Cohen, J.A., additional, Coles, A.J., additional, Confavreux, C., additional, Fox, E.J., additional, Hartung, H.-P., additional, Havrdova, E., additional, Selmaj, K.W., additional, Weiner, H.L., additional, Brinar, V., additional, Giovannoni, G., additional, Stojanovic, M., additional, Cinar, A., additional, Margolin, D.H., additional, Panzara, M., additional, and Compston, D.A.S., additional

Published
2013
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16. Alemtuzumab treatment has no adverse impact on sperm quality, quantity, or motility: A CARE-MS substudy

Author

Margolin, D.H., primary, Rizzo, M.A., additional, Smith, G., additional, Arnold, D.L., additional, Cohen, J.A., additional, Coles, A.J., additional, Confavreux, C., additional, Fox, E.J., additional, Hartung, H.-P., additional, Havrdova, E., additional, Selmaj, K.W., additional, Weiner, H.L., additional, Brinar, V., additional, Giovannoni, G., additional, Miller, T.A., additional, Stojanovic, M., additional, Twyman, C.L., additional, Lake, S.L., additional, Panzara, M., additional, and Compston, D.A.S., additional

Published
2013
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17. Efficacy and Safety Results from Comparison of Alemtuzumab and Rebif(R) Efficacy in Multiple Sclerosis II (CARE-MS II): A Phase 3 Study in Relapsing-Remitting Multiple Sclerosis Patients Who Relapsed on Prior Therapy (S01.004)

Author

Cohen, J., primary, Twyman, C., additional, Arnold, D., additional, Coles, A., additional, Confavreux, C., additional, Fox, E., additional, Hartung, H., additional, Havrdova, E., additional, Selmaj, K., additional, Weiner, H., additional, Miller, T., additional, Lake, S., additional, Margolin, D., additional, Panzara, M., additional, and Compston, A., additional

Published
2012
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18. Incidence of Autoimmunity in a Phase 3 Trial: Comparison of Alemtuzumab and Rebif(R) in Multiple Sclerosis I (CARE-MS I) (S41.006)

Author

Selmaj, K., primary, Arnold, D., additional, Brinar, V., additional, Cohen, J., additional, Coles, A., additional, Confavreux, C., additional, Fox, E., additional, Giovannoni, G., additional, Hartung, H., additional, Havrdova, E., additional, Stojanovic, M., additional, Weiner, H., additional, Lake, S., additional, Margolin, D., additional, Oyuela, P., additional, Panzara, M., additional, and Compston, A., additional

Published
2012
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19. Relapse Outcomes with Alemtuzumab vs. Rebif(R) in Treatment-Naive Relapsing-Remitting Multiple Sclerosis (CARE-MS I): Secondary and Tertiary Endpoints (PD5.004)

Author

Fox, E., primary, Arnold, D., additional, Brinar, V., additional, Cohen, J., additional, Coles, A., additional, Confavreux, C., additional, Giovannoni, G., additional, Hartung, H., additional, Havrdova, E., additional, Selmaj, K., additional, Stojanovic, M., additional, Weiner, H., additional, Lake, S., additional, Margolin, D., additional, Panzara, M., additional, and Compston, A., additional

Published
2012
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20. Efficacy and Safety Results from Comparison of Alemtuzumab and Rebif(R) Efficacy in Multiple Sclerosis I (CARE-MS I): A Phase 3 Study in Relapsing-Remitting Treatment-Naive Patients (S01.006)

Author

Coles, A., primary, Brinar, V., additional, Arnold, D., additional, Cohen, J., additional, Confavreux, C., additional, Fox, E., additional, Hartung, H., additional, Havrdova, E., additional, Selmaj, K., additional, Weiner, H., additional, Giovannoni, G., additional, Stojanovic, M., additional, Lake, S., additional, Margolin, D., additional, Panzara, M., additional, and Compston, A., additional

Published
2012
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21. Effect of Alemtuzumab vs. Rebif(R) on Brain MRI Measurements: Results of CARE-MS I, a Phase 3 Study (S11.006)

Author

Arnold, D., primary, Brinar, V., additional, Cohen, J., additional, Coles, A., additional, Confavreux, C., additional, Fisher, E., additional, Fox, E., additional, Giovannoni, G., additional, Hartung, H., additional, Havrdova, E., additional, Selmaj, K., additional, Weiner, H., additional, Stojanovic, M., additional, Lake, S., additional, Margolin, D., additional, Panzara, M., additional, and Compston, A., additional

Published
2012
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22. Infections in Phase 3 Study: Comparison of Alemtuzumab and Rebif(R) Efficacy in Multiple Sclerosis I (CARE-MS I) (S41.007)

Author

Havrdova, E., primary, Arnold, D., additional, Cohen, J., additional, Coles, A., additional, Confavreux, C., additional, Fox, E., additional, Hartung, H., additional, Selmaj, K., additional, Weiner, H., additional, Brinar, V., additional, Giovannoni, G., additional, Stojanovic, M., additional, Lake, S., additional, Margolin, D., additional, Oyuela, P., additional, Panzara, M., additional, and Compston, A., additional

Published
2012
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23. GLANCE

Author

Goodman, A. D., primary, Rossman, H., additional, Bar-Or, A., additional, Miller, A., additional, Miller, D. H., additional, Schmierer, K., additional, Lublin, F., additional, Khan, O., additional, Bormann, N. M., additional, Yang, M., additional, Panzara, M. A., additional, and Sandrock, A. W., additional

Published
2009
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24. Effect of plasma exchange in accelerating natalizumab clearance and restoring leukocyte function

Author

Khatri, B. O., primary, Man, S., additional, Giovannoni, G., additional, Koo, A. P., additional, Lee, J-C, additional, Tucky, B., additional, Lynn, F., additional, Jurgensen, S., additional, Woodworth, J., additional, Goelz, S., additional, Duda, P. W., additional, Panzara, M. A., additional, Ransohoff, R. M., additional, and Fox, R. J., additional

Published
2009
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25. The incidence and significance of anti-natalizumab antibodies

Author

Calabresi, P. A., primary, Giovannoni, G., additional, Confavreux, C., additional, Galetta, S. L., additional, Havrdova, E., additional, Hutchinson, M., additional, Kappos, L., additional, Miller, D. H., additional, O'Connor, P. W., additional, Phillips, J. T., additional, Polman, C. H., additional, Radue, E. -W., additional, Rudick, R. A., additional, Stuart, W. H., additional, Lublin, F. D., additional, Wajgt, A., additional, Weinstock-Guttman, B., additional, Wynn, D. R., additional, Lynn, F., additional, and Panzara, M. A., additional

Published
2007
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27. Natalizumab reduces visual loss in patients with relapsing multiple sclerosis

Author

Balcer, L. J., primary, Galetta, S. L., additional, Calabresi, P. A., additional, Confavreux, C., additional, Giovannoni, G., additional, Havrdova, E., additional, Hutchinson, M., additional, Kappos, L., additional, Lublin, F. D., additional, Miller, D. H., additional, O'Connor, P. W., additional, Phillips, J. T., additional, Polman, C. H., additional, Radue, E. -W., additional, Rudick, R. A., additional, Stuart, W. H., additional, Wajgt, A., additional, Weinstock-Guttman, B., additional, Wynn, D. R., additional, Lynn, F., additional, and Panzara, M. A., additional

Published
2007
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28. Infusion-related hypersensitivity reactions during natalizumab treatment

Author

Phillips, J. T., primary, O’Connor, P. W., additional, Havrdova, E., additional, Hutchinson, M., additional, Kappos, L., additional, Miller, D. H., additional, Polman, C. H., additional, Lublin, F. D., additional, Giovannoni, G., additional, Wajgt, A., additional, Lynn, F., additional, Panzara, M. A., additional, and Sandrock, A. W., additional

Published
2006
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30. Assessing disability progression with the Multiple Sclerosis Functional Composite.

Author

Rudick, R. A., Polman, C. H., Cohen, J. A., Walton, M. K., Miller, A. E., Confavreux, C., Lublin, F. D., Hutchinson, M., O'Connor, P. W., Schwid, S. R., Balcer, L. J., Lynn, F., Panzara, M. A., and Sandrock, A. W.

Subjects
MULTIPLE sclerosis, DEVELOPMENTAL disabilities, MYELIN sheath diseases, VIRUS diseases, ANTINEOPLASTIC agents, GLYCOPROTEINS
Abstract

Background The initial Multiple Sclerosis Functional Composite (MSFC) proposal was a three-part composite of quantitative measures of ambulation, upper extremity function, and cognitive function expressed as a single composite Z-score. However, the clinical meaning of an MSFC Z-score change is not obvious. This study instead used MSFC component data to define a patient-specific disease progression event. Objective Evaluate a new method for analyzing disability progression using the MSFC. Methods MSFC progression was defined as worsening from baseline on scores of at least one MSFC component by 20% (MSFC Progression-20) or 15% (MSFC Progression-15), sustained for ≥3 months. Progression rates were determined using data from natalizumab clinical studies (Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis [AFFIRM] and Safety and Efficacy of Natalizumab in Combination With Interferon Beta-1a in Patients With Relapsing Remitting Multiple Sclerosis [SENTINEL]). Correlations between MSFC progression and other clinical measures were determined, as was sensitivity to treatment effects. Results Substantial numbers of patients met MSFC progression criteria, with MSFC Progression-15 being more sensitive than MSFC Progression-20, at both 1 and 2 years. MSFC Progression-20 and MSFC Progression-15 were related significantly to Expanded Disability Status Scale (EDSS) score change, relapse rate, and the SF-36 Physical Component Summary (PCS) score change. MSFC Progression-20 and MSFC Progression-15 at 1 year were predictive of EDSS progression at 2 years. Both MSFC progression end points demonstrated treatment effects in AFFIRM, and results were replicated in SENTINEL. Conclusion MSFC Progression-20 and MSFC Progression-15 are sensitive measures of disability progression; correlate with EDSS, relapse rates, and SF-36 PCS; and are capable of demonstrating therapeutic effects in randomized, controlled clinical studies. [ABSTRACT FROM AUTHOR]

Published
2009
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31. Repeated assessment of neuropsychological deficits in multiple sclerosis using the Symbol Digit Modalities Test and the MS Neuropsychological Screening Questionnaire.

Author

Benedict, R. H. B., Duquin, J. A., Jurgensen, S., Rudick, R. A., Feitcher, J., Munschauer, F. E., Panzara, M. A., and Weinstock-Guttman, B.

Subjects
MULTIPLE sclerosis, MYELIN sheath diseases, DEMYELINATION, VIRUS diseases, CLINICAL trials, PATIENTS, DIAGNOSIS
Abstract

Background Brief cognitive performance tests and self-report measures of neuropsychological symptoms have been proposed for screening purposes in multiple sclerosis (MS) clinics. To better understand the reliability of screening methods, two tests, the Symbol Digit Modalities Test (SDMT) and the MS Neuropsychological Screening Questionnaire (MSNQ), were administered to 76 patients with MS and 25 healthy controls, matched on demographic characteristics. Methods Tests were administered at monthly intervals, over 6 months. In addition, the Beck Depression Inventory Fast Screen for medical patients (BDIFS) was administered to monitor for changes in depression. Our objectives were to determine the reliability of these measures and the relative contribution of cognitive impairment and depression in predicting self-report MSNQ scores. Results Results showed that both the SDMT and MSNQ have good to excellent reproducibility over repeated testing. In MS, there are minimal practice effects over successive tests, in the order of 0.2 SD for SDMT and minimal change in the MSNQ. Regression analyses modeled to predict MSNQ based on SDMT and BDIFS showed significant contribution for both, but with the majority of variance being accounted for depression. Conclusions We conclude that these brief screening tests provide some independent information about the mental status of patients with MS and are reliable, even when used in monthly, successive examinations. [ABSTRACT FROM AUTHOR]

Published
2008
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32. MRI outcomes in a placebo-controlled trial of natalizumab in relapsing MS

Author

Miller, D H., Soon, D, Fernando, K T., MacManus, D G., Barker, G J., Yousry, T A., Fisher, E, O'Connor, P W., Phillips, J T., Polman, C H., Kappos, L, Hutchinson, M, Havrdova, E, Lublin, F D., Giovannoni, G, Wajgt, A, Rudick, R, Lynn, F, Panzara, M A., and Sandrock, A W.

Abstract

In a 2-year, placebo-controlled trial (the Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis AFFIRM study), involving 942 patients with relapsing multiple sclerosis (MS), natalizumab significantly reduced the relapse rate by 68% and progression of sustained disability by 42% vs placebo. We report the effect of natalizumab on MRI measures from the AFFIRM study.

Published
2007
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37. The role of autoimmune t lymphocytes in the pathogenesis of multiple sclerosis

Author

Hohlfeld, R., Meinl, E., Weber, F., Zipp, F., Schmidt, S., Sotgiu, S., Goebels, N., Voltz, R., Spuler, S., Iglesias, A., Wekerle, H., Staudt, L. M., Lenardo, M. J., Matis, L. A., Germain, R. N., Margulies, D. H., Bjorkman, P. J., Saper, M. A., Samraoui, B., Brown, J. H., Jardetzky, T. S., Gorga, J. C., Ben-Nun, A., Cohen, I. R., Toyka, K. V., Heininger, K., Drexler, K., Fleckenstein, B., Allegretta, M., Nicklas, J. A., Sriram, S., Albertini, R. J., Ofosu-Appiah, W., Mokhtarian, F., Miller, A., Grob, D., Zhang, J., Markovic, S., Lacet, B., Oksenberg, J. R., Panzara, M. A., Begovich, A. B., Kojima, K., Lannes-Vieira, J., Lassmann, H., Fritz Zimprich, Rossler, K., Berger, T., Wucherpfennig, K. W., Weiner, H. L., Hafler, D. A., Martin, R., Mcfarland, H. F., Mcfarlin, D. E., Uematsu, Y., Wege, H., Straus, A., Salvetti, M., Ristori, G., D Amato, M., Witek, C., Selmaj, K., Brosnan, C. F., Raine, C. S., Battistini, L., Kowal, C., Arnason, B. G. W., Steinman, L., Medaer, R., Stinissen, P., Bourdette, D. N., Whitham, R. H., Chou, Y. K., and Friedman, A.

45. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis.

Author

Hauser SL, Waubant E, Arnold DL, Vollmer T, Antel J, Fox RJ, Bar-Or A, Panzara M, Sarkar N, Agarwal S, Langer-Gould A, Smith CH, HERMES Trial Group, Hauser, Stephen L, Waubant, Emmanuelle, Arnold, Douglas L, Vollmer, Timothy, Antel, Jack, Fox, Robert J, and Bar-Or, Amit

Abstract

Background: There is increasing evidence that B lymphocytes are involved in the pathogenesis of multiple sclerosis, and they may be a therapeutic target. Rituximab, a monoclonal antibody, selectively targets and depletes CD20+ B lymphocytes.Methods: In a phase 2, double-blind, 48-week trial involving 104 patients with relapsing-remitting multiple sclerosis, we assigned 69 patients to receive 1000 mg of intravenous rituximab and 35 patients to receive placebo on days 1 and 15. The primary end point was the total count of gadolinium-enhancing lesions detected on magnetic resonance imaging scans of the brain at weeks 12, 16, 20, and 24. Clinical outcomes included safety, the proportion of patients who had relapses, and the annualized rate of relapse.Results: As compared with patients who received placebo, patients who received rituximab had reduced counts of total gadolinium-enhancing lesions at weeks 12, 16, 20, and 24 (P<0.001) and of total new gadolinium-enhancing lesions over the same period (P<0.001); these results were sustained for 48 weeks (P<0.001). As compared with patients in the placebo group, the proportion of patients in the rituximab group with relapses was significantly reduced at week 24 (14.5% vs. 34.3%, P=0.02) and week 48 (20.3% vs. 40.0%, P=0.04). More patients in the rituximab group than in the placebo group had adverse events within 24 hours after the first infusion, most of which were mild-to-moderate events; after the second infusion, the numbers of events were similar in the two groups.Conclusions: A single course of rituximab reduced inflammatory brain lesions and clinical relapses for 48 weeks. This trial was not designed to assess long-term safety or to detect uncommon adverse events. The data provide evidence of B-cell involvement in the pathophysiology of relapsing-remitting multiple sclerosis. (ClinicalTrials.gov number, NCT00097188 [ClinicalTrials.gov].). [ABSTRACT FROM AUTHOR]

Published
2008
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46. Progressive MS Alliance Industry Forum: Maximizing Collective Impact To Enable Drug Development

Author

Paola Zaratin, Kathryn E Smith, Alan J. Thompson, G. Comi, M. Panzara, Timothy Coetzee, K. Ramsey, Zaratin, P, Comi, Giancarlo, Coetzee, T, Ramsey, K, Smith, K, Thompson, A, and Panzara, M.

Subjects
0301 basic medicine, Pharmacology, Progressive multiple sclerosis, Biomedical Research, Process management, Drug Industry, education, Multiple Sclerosis, Chronic Progressive, Toxicology, Collective impact, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Alliance, Drug development, Drug Design, Drug Discovery, Humans, Business, Cooperative Behavior, health care economics and organizations, 030217 neurology & neurosurgery
Abstract

The Progressive MS Alliance Industry Forum describes a new approach to address barriers to developing treatments for progressive multiple sclerosis (MS). This innovative model promises to facilitate robust collaboration between industry, academia, and patient organizations and accelerate research towards the overarching goal of developing safe and effective treatments for progressive MS.

Published
2016
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47. GLANCE: results of a phase 2, randomized, double-blind, placebo-controlled study.

Author

Goodman AD, Rossman H, Bar-Or A, Miller A, Miller DH, Schmierer K, Lublin F, Khan O, Bormann NM, Yang M, Panzara MA, and Sandrock AW

Subjects
Adult, Antibodies, Monoclonal adverse effects, Antibodies, Monoclonal immunology, Antibodies, Monoclonal, Humanized, Double-Blind Method, Drug Interactions, Drug Therapy, Combination, Female, Glatiramer Acetate, Humans, Hypersensitivity immunology, Magnetic Resonance Imaging methods, Male, Middle Aged, Multiple Sclerosis, Relapsing-Remitting complications, Multiple Sclerosis, Relapsing-Remitting diagnostic imaging, Natalizumab, Peptides adverse effects, Radiography, Antibodies, Monoclonal administration & dosage, Multiple Sclerosis, Relapsing-Remitting drug therapy, Peptides administration & dosage
Abstract

Objective: To evaluate the safety and tolerability of natalizumab when added to glatiramer acetate (GA) in patients with relapsing multiple sclerosis. The primary outcome assessed whether this combination would increase the rate of development of new active lesions on cranial MRI scans vs GA alone., Methods: This phase 2, randomized, double-blind, placebo-controlled study included patients aged 19 to 55 years who were treated with GA for at least 1 year before randomization and experienced at least one relapse during the previous year. Patients received IV natalizumab 300 mg (n = 55) or placebo (n = 55) once every 4 weeks plus GA 20 mg subcutaneously once daily for < or = 20 weeks., Results: The mean rate of development of new active lesions was 0.03 with combination therapy vs 0.11 with GA alone (p = 0.031). Combination therapy resulted in lower mean numbers of new gadolinium-enhancing lesions (0.6 vs 2.3 for GA alone, p = 0.020) and new/newly enlarging T2-hyperintense lesions (0.5 vs 1.3, p = 0.029). The incidence of infection and infusion reactions was similar in both groups; no hypersensitivity reactions were observed. One serious adverse event occurred with combination therapy (elective hip surgery). With the exception of an increase in anti-natalizumab antibodies with combination therapy, laboratory data were consistent with previous clinical studies of natalizumab alone., Conclusion: The combination of natalizumab and glatiramer acetate seemed safe and well tolerated during 6 months of therapy.

Published
2009
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48. T cell receptor BV gene rearrangements in the spinal cords and cerebrospinal fluid of patients with amyotrophic lateral sclerosis.

Author

Panzara MA, Gussoni E, Begovich AB, Murray RS, Zang YQ, Appel SH, Steinman L, and Zhang J

Subjects
Adult, Aged, Aged, 80 and over, Amino Acid Sequence, Autopsy, Female, Genes, T-Cell Receptor beta, HLA-D Antigens genetics, Histocompatibility Testing, Humans, Male, Middle Aged, Molecular Sequence Data, Motor Neuron Disease cerebrospinal fluid, Receptors, Antigen, T-Cell, alpha-beta chemistry, Reference Values, Reverse Transcriptase Polymerase Chain Reaction, Spinal Cord pathology, Transcription, Genetic, Gene Rearrangement, beta-Chain T-Cell Antigen Receptor, Motor Neuron Disease genetics, Motor Neuron Disease immunology, Receptors, Antigen, T-Cell, alpha-beta genetics, Spinal Cord immunology, T-Lymphocytes immunology
Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal disorder whose etiology and pathogenesis remain unknown. Recent studies, however, have demonstrated the presence of inflammatory infiltrates within ALS spinal cord and suggested the possibility of an immune-mediated process in motor neuron degeneration. We have analyzed the diversity of T-cells in the spinal cord in ALS. Reverse transcriptase polymerase chain reaction (RT-PCR) with variable (V) region sequence specific oligonucleotide primers was used to amplify T-cell receptor (TCR)BV transcripts from spinal cords obtained at autopsy from patients with ALS, patients who died without inflammatory disease of the central nervous system, brains from patients with ALS, and brains from patients who died with inflammatory CNS disease. Sequencing was then performed on the amplified transcripts. An overall increase in the level of TCRBV 2 transcripts was detected in ALS specimens when compared to controls. This result was independent of the HLA genotype of the individual. Furthermore, enrichment of TCRBV2-positive T cells could be demonstrated in cerebrospinal fluid derived from patients with ALS, using PCR analysis and a T cell stimulation assay with toxic shock syndrome toxin-1 (TSST-1), a Vbeta2-specific superantigen. Our results suggest that an immunological process involving the specific expansion of Vbeta2 TCR-positive T-cells may be important in the pathogenesis of ALS., (Copyright 1999 Academic Press.)

Published
1999
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49. Multiple sclerosis: from immunogenetics to immunotherapy.

Author

Oksenberg JR, Panzara MA, and Steinman L

Subjects
Animals, Antigens immunology, Binding, Competitive, Genes, Genetic Predisposition to Disease, Humans, Major Histocompatibility Complex physiology, Multiple Sclerosis genetics, Peptides immunology, Receptors, Antigen, T-Cell immunology, Vaccination, Immunotherapy, Multiple Sclerosis immunology, Multiple Sclerosis therapy
Published
1993
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50. Selection for T-cell receptor V beta-D beta-J beta gene rearrangements with specificity for a myelin basic protein peptide in brain lesions of multiple sclerosis.

Author

Oksenberg JR, Panzara MA, Begovich AB, Mitchell D, Erlich HA, Murray RS, Shimonkevitz R, Sherritt M, Rothbard J, Bernard CC, and Steinman L

Subjects
Amino Acid Sequence, Animals, Base Sequence, Brain pathology, Cloning, Molecular, Encephalomyelitis, Autoimmune, Experimental genetics, Encephalomyelitis, Autoimmune, Experimental immunology, HLA-D Antigens analysis, Humans, Molecular Sequence Data, Multiple Sclerosis pathology, Oligodeoxyribonucleotides, Phenotype, Polymerase Chain Reaction methods, RNA, Messenger genetics, Rats, Spinal Cord immunology, T-Lymphocytes immunology, Brain immunology, CD3 Complex genetics, Gene Rearrangement, beta-Chain T-Cell Antigen Receptor, HLA-D Antigens genetics, Multiple Sclerosis genetics, Multiple Sclerosis immunology, Myelin Basic Protein immunology
Abstract

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system in which a restricted cellular immune response has been observed. In order to establish whether such T cell responses are likely to be antigen-specific particularly with regard to myelin basic protein (MBP), we analysed T-cell receptor (TCR) gene rearrangements directly from MS brain plaques, using the polymerase chain reaction on reverse transcribed messenger RNA, and compared these with TCR of previously described MBP-specific T cell clones from MS and the rat model experimental allergic encephalomyelitis. Rearranged V beta 5.2 genes were detected in the brains of all patients who were HLA DRB1*1501, DQA1*0102, DQB1*0602, DPB1*0401. The V beta 5.2-D beta-J beta sequences in these MS brain plaques revealed five motifs. One of the common motifs was identical to that described for the VDJ region of a V beta 5.2 T-cell clone. This clone was from an MS patient who was HLA DRB1*1501, DQB1*0602, DPB1*0401, and it was cytotoxic towards targets containing the MBP peptide 89-106 (ref. 1). The deduced amino-acid sequence of this VDJ rearrangement, Leu-Arg-Gly, has also been described in rat T cells cloned from experimental allergic encephalomyelitis lesions, which are specific for MBP peptide 87-99 (ref. 2). VDJ sequences with specificity for this MBP epitope constitute a large fraction (40%) of the TCR V beta 5.2 N(D)N rearrangements in MS lesions. The capacity of rat T cells with these VDJ sequences to cause experimental allergic encephalomyelitis and the prevalence of such sequences in demyelinated human lesions indicate that T cells with this rearranged TCR may be critical in MS.

Published
1993
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