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2. Prediction of survival in amyotrophic lateral sclerosis: a nationwide, Danish cohort study

Author

Kjældgaard, Anne-Lene, Pilely, Katrine, Olsen, Karsten Skovgaard, Jessen, Anders Hedegaard, Lauritsen, Anne Øberg, Pedersen, Stephen Wørlich, Svenstrup, Kirsten, Karlsborg, Merete, Thagesen, Helle, Blaabjerg, Morten, Theódórsdóttir, Ásta, Elmo, Elisabeth Gundtoft, Møller, Anette Torvin, Bonefeld, Lone, Berg, Mia, Garred, Peter, and Møller, Kirsten

Published
2021
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3. Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS

Author

Miller, Timothy M, Cudkowicz, Merit E, Andrews, Jinsy A, Hesters, Adele, Kermorvant, Hugo, Lacomblez, Lucette, Forestier, Nadine Le, Lenglet, Thimotée, Retail, Maryvonne, Ruiz Del Mar Amador, Maria, Salachas, François, Shotar, Eimad, Sourour, Nader, Babu, Suma, Dorst, Johannes, Froehlich, Elke, Fromm, Andrea, Kandler, Katharina, Langer, Eva, Leichtle, Sarah, Ludolph, Albert, Mayer, Kristina, Michels, Sebastian, Raubold, Sabine, Benatar, Michael, Schuster, Joachim, Weiland, Ulrike, Wiesenfarth, Maximilian, Witzel, Simon, Calvo, Andrea, Canosa, Antonio, Casale, Federico, Chiò, Adriano, Fuda, Giuseppe, Grassano, Maurizio, McDermott, Christopher J, Marchese, Giulia, Moglia, Cristina, Palumbo, Francesca, Salamone, Paolina, Ajiki, Takahiro, Akasaka, Aya, Ando, Masahiro, Arata, Hitoshi, Asuka, Kitamura, Baba, Kosuke, Cochrane, Thos, Bekku, Goichi, Chiba, Tomoya, Date, Yugaku, Eriko, Takeuchi, Hashiguchi, Akihiro, Hatatori, Ritsuko, Hayano, Eri, Hayashi, Yuto, Higashi, Keiko, Higuchi, Eriko, Chary, Sowmya, Hiramatsu, Yu, Horikawa, Rui, Ikenaka, Kensuke, Ishiura, Hiroyuki, Ito, Daisuke, Kawai, Sachiko, Kikuchi, Junko, Kuzuyama, Haruko, Li, Xuehong, Matsumoto, Chika, Chew, Sheena, Matsuura, Eiji, Michizono, Kumiko, Mitsui, Jun, Mitsutake, Akihiko, Mochizuki, Hideki, Nagamatsu, Akemi, Nagano, Seiichi, Nakamura, Tomonori, Naruse, Hiroya, Ogasawara, Asuka, Zhu, Han, Okada, Kensuke, Okamoto, Yuji, Okuno, Tatsusada, Oyama, Satoshi, Ozono, Tatsuhiko, Sakiyama, Yusuke, Sakuishi, Kaori, Seki, Morinobu, Shibata, Shota, Shimizu, Mikito, Wu, Fan, Takahata, Katsunori, Takahito, Yoshizaki, Takashima, Hiroshi, Takeichi, Hiroko, Tashiro, Yuichi, Toda, Tatsushi, Tomizu, Yuki, Tomoya, Wadayama, Ujiakira, Nishiike, Yashita, Daiki, Nestorov, Ivan, Al-Chalabi, Ammar, Alix, James, Bangalore, Priyadarshini, Blackburn, Daniel, Chiwera, Theresa, Clegg, Rosie, Collins, Alexis, Cooper-Knock, Jonathan, Emery, Anna, Franklin, John, Genge, Angela, Graham, Danielle, Green, Louisa, Harvey, Callum, Hobson, Esther, Islam, Mahjabim, Jenkins, Thomas Michael, Kazoka, Mbombe, Kelly, Gillian, Korley, Mercy, Madarshahaian, Daniel, Mayl, Keith, Sun, Peng, McDermott, Christopher John, Radford, Alex, Shaw, Christopher, Shaw, Pamela J, Sidebottom, Joe, Smart, Lynne, Sreedharan, Jemeen, Stone, Ben, Tsironis, Theocharis, Tuddenham, Lee, McNeill, Manjit, Verber, Nick, Wollff, Helen, Young, Stacy, Zis, Panagiotis, Adamo, Ashley, Ahmed, Arubah, Ajroud-Driss, Senda, Alameda, Gustave, Arcila-Londono, Ximena, Fanning, Laura, Baird, Candy, Bazan, Tracy, Berry, James, Bordeau, Jane, Bradford, Wendy, Brook, Nyda, Brown, Lauren, Bucelli, Robert C, Ferguson, Toby A, Buckner, Katherine, Budler, Michael W, Burba, Lindita, Burke, Katherine, Calhoun, Ashley D, Campbell, Sarah, Carey, Judith, Caristo, Irys B, Carty, Simon, Chan, Emmanuel, Fradette, Stephanie, Chaudhry, Vinay, Chen, Ricky, Chow, Saephanh, Clawson, Lora L, Clemens, Mitchell, Cloninger, Suzann E, Coleman-Wood, Krista, Cooper, Thomas N, Cummings, Arlena, Daniels, Jacquelyn, VALOR, DeSaro, Pamela, DeWitt, Michelle, Dedi, Brixhilda, Dempsey, Debbie, Denny, Carol, Doherty, Jenna, Doherty, Leana, Donahue, Megan, Doyle, Michael, Duncan, Jessie, Group, OLE Working, Elman, Lauren, Eloge, Christine M, Echiti, Desirae R, Ferrey, Dominic, Fournier, Christina, Fukumura, Yuriko, Gallagher, Katherine, Garaycoa, Jessica, Garrett, Mark, Gibson, Richard L, Beullens, Lien, Gifford, Ryan, Glass, Jonathan D, Gogol, Danuta, Golden, Shea, Gonzalez, Alexa, Goodman, Ira, Goolsby, Christopher, Goslin, Kimberly, Goulbourne, Michael, Granit, Volkan, Claeys, Kristl, Grignon, Anne-Laure, GuhaRay, Adreeja, Guide, Debra, Gundogdu, Melek Betul, Gutierrez, Gil, Hastings, Debbie, Hayzen, Colleen, Herzog, Hilary, Holloway, Raegan, Jacobs, Gabriel, Claeys, Thomas, Jacobsen, Bill, James, Virginia, Jenkins, Liberty, Jockel-Balsarotti, Jennifer, Johnson, Linda Carol, Jose, Sunil, Joslin, Benjamin, Karanja, Elizabeth, Katz, Jonathan, Keener, Anthony, Couwelier, Goedele, Kittle, Gale, Klein, Sara, Kreple, Collin, Rebecca, Rebecca, Kuenzler, Kuenzler, Kusnir, Jorge, Labbe, Kristen, Lachica-Encinas, Nicolet, Ladha, Shafeeq, Leimer, Lesli, D'Hondt, Ann, Levy, Michael, Levy, Wendy, Li, Yingji, Likanje, Marie-France, Livigni, Rebecca, Locatelli, Eduardo, Luppino, Sarah, Malcolm, Amber, Maragakis, Nicholas, Marin, Horia, Debien, Elisa, Markowitz, Clyde, Markway, Jesse, McCaffrey, Alexandra, McCoy, Arita, McCoy Gross, Kelly, Mehta, Kush, Meyer, Robert, Milan, Jennifer, Miller, Timothy, Miller, Robert G, de Keersmaecker, Sebastiaan, Morales, Francisco, Mosmiller, Elizabeth, Mott, Donovan, Moulton, Kelsey, Murphy, Christine A, Negron, Tirso, Nelson, Cassandra, Newman, Daniel S, Nissinen, Janne Kristoffer, Norman, Andrew, Della Faille, Laetitia, Ohkubo, Takuya, Olney, Nicholas, Ortiz, Natasha, Oskarsson, Bjorn, Pace, Mitchell, Packard, Kathleen, Padgett, Denny, Paganoni, Sabrina, Paredes, Maria E, Parker, Elizabeth, Delmotte, Koen, Partlow, Ann, Pattee, Gary L, Paulett, Jany, Pelot, Antoinette, Pfeifer, Kyle M, Pijanowski, Olivia, Pioro, Erik, Polak, Meraida, Prakash, Ahalya, Previte, Rosemarie, Depoortere, Sofie, Pukenas, Bryan, Quinn, Colin, Ravits, John, Razavi, Ryan, Regan, Tyler, Riley, Kristen M, Roth, Heather, Sanders, Danica, Scalia, Jennifer, Schmidt, Emma, de Velder, Laura, Schwen, Edward, Shah, Jaimin, Shah, Stuti, Shefner, Jeremy, Sheldon, Danielle, Simmons, Karon, Singh, Navneet K, Singleton, Jessica, Smiley, Richard, Smith, William B, Dobbels, Laurens, Smith, Sean, Sotirchos, Elias, Sorenson, Eric, Staff, Nathan, Steele, Julie, Steijlen, Kara, Stirrat, Taylor, Stoica, George S, Strong, Stephanie, Sufit, Robert, Sobue, Gen, Gijs, Jeroen, Sultze, Jane, Swartz, Amy, Szymanski, April, Tay, Anna, Thakore, Nimish, Thiessen, Diana, Thotala, Sukrutha, Trudell, Randall G, Turcotte, Nicole, Turner, Michelle, Horckmans, Simon, Uchil, Alpa, Upadhyay, Vihar, Usman, Uzma, Vallis, Anne, Vaporean-Bussey, Danielle, Vladimirova, Valentine, Weber, Harli, Winbigler, Jennifer, Wojanowski, Heather, Wulf, Charlie, Lamaire, Nikita, Yasek, Julia, Yoo, Stephanie, Zivalic, Hannah, Cole, Alexandra, File, Greta, Foate, Jeremy, Mason, Deborah, Newton, Susan, Roberts, Stephen, Sellwood, Cory Dean, Liessens, Hannelore, Swan, James, Werno, Anja, Zhong, Cathy, Masrori, Pegah, Nysten, Celine, Schotte, Caroline, Serrien, Anouk, Swinnen, Bart, Tilkin, Petra, van Daele, Sien, Van Damme, Philip, Vynckier, Jan, Wouters, Anke, Abrahao, Agessandro, Angle, Mark, Badawy, Mohamed, Berube, Maxime, Bertone, Vanessa, Cooper, Sarah Marie, Dobrowolski, Peter, Fong, Helen, Hannouche, Matthew, Hartley, Denise, Hogan, Michael, Johnston, Wendy, Khalfallah, Yousra, Korngut, Lawrence, Kroetsch, Gina, Letourneau, Justin, Magnussen, Claire, Martinez, Jose, Massie, Rami, Mobach, Theodore, Mookshah, Jahan, Ozelsel, Timur, Parks, Andrea, Petrillo, Janet, Pfeffer, Gerald, Ludolph, Albert C, Pham, Shirley, Phung, Liane, Shiungsun, Rodney, Pi-Shan, Li, Santos, Denizart, Salmon, Kristiana, Saunders, Natalie, Sembinelli, Dylan, Tymkow, Kelsey, Wong, Berchman, Zinman, Lorne, Karlsborg, Merete, Pedersen Lomholt, Therese, Nilsson, Sigrid, Salvesen, Lisette, Skov, Pernille, Svenstrup, Kristen, Bruneteau, Gaelle, Calerencon, Frederic, and Guimaraes Costa, Raquel

Subjects
Adult, drug effects [Recovery of Function], Spinal, Oligonucleotides, blood [Neurofilament Proteins], administration & dosage [Oligonucleotides, Antisense], tofersen, Injections, blood [Amyotrophic Lateral Sclerosis], pharmacology [Oligonucleotides, Antisense], Superoxide Dismutase-1, Double-Blind Method, Neurofilament Proteins, Humans, ddc:610, Antisense, Injections, Spinal, Biomarkers, Recovery of Function, Amyotrophic Lateral Sclerosis, Oligonucleotides, Antisense, blood [Biomarkers], drug therapy [Amyotrophic Lateral Sclerosis], therapeutic use [Oligonucleotides, Antisense], SOD1 protein, human, General Medicine, genetics [Superoxide Dismutase-1], genetics [Amyotrophic Lateral Sclerosis], cerebrospinal fluid [Biomarkers], cerebrospinal fluid [Superoxide Dismutase-1], cerebrospinal fluid [Amyotrophic Lateral Sclerosis]
Abstract

The intrathecally administered antisense oligonucleotide tofersen reduces synthesis of the superoxide dismutase 1 (SOD1) protein and is being studied in patients with amyotrophic lateral sclerosis (ALS) associated with mutations in SOD1 (SOD1 ALS).In this phase 3 trial, we randomly assigned adults with SOD1 ALS in a 2:1 ratio to receive eight doses of tofersen (100 mg) or placebo over a period of 24 weeks. The primary end point was the change from baseline to week 28 in the total score on the ALS Functional Rating Scale-Revised (ALSFRS-R; range, 0 to 48, with higher scores indicating better function) among participants predicted to have faster-progressing disease. Secondary end points included changes in the total concentration of SOD1 protein in cerebrospinal fluid (CSF), in the concentration of neurofilament light chains in plasma, in slow vital capacity, and in handheld dynamometry in 16 muscles. A combined analysis of the randomized component of the trial and its open-label extension at 52 weeks compared the results in participants who started tofersen at trial entry (early-start cohort) with those in participants who switched from placebo to the drug at week 28 (delayed-start cohort).A total of 72 participants received tofersen (39 predicted to have faster progression), and 36 received placebo (21 predicted to have faster progression). Tofersen led to greater reductions in concentrations of SOD1 in CSF and of neurofilament light chains in plasma than placebo. In the faster-progression subgroup (primary analysis), the change to week 28 in the ALSFRS-R score was -6.98 with tofersen and -8.14 with placebo (difference, 1.2 points; 95% confidence interval [CI], -3.2 to 5.5; P = 0.97). Results for secondary clinical end points did not differ significantly between the two groups. A total of 95 participants (88%) entered the open-label extension. At 52 weeks, the change in the ALSFRS-R score was -6.0 in the early-start cohort and -9.5 in the delayed-start cohort (difference, 3.5 points; 95% CI, 0.4 to 6.7); non-multiplicity-adjusted differences favoring early-start tofersen were seen for other end points. Lumbar puncture-related adverse events were common. Neurologic serious adverse events occurred in 7% of tofersen recipients.In persons with SOD1 ALS, tofersen reduced concentrations of SOD1 in CSF and of neurofilament light chains in plasma over 28 weeks but did not improve clinical end points and was associated with adverse events. The potential effects of earlier as compared with delayed initiation of tofersen are being further evaluated in the extension phase. (Funded by Biogen; VALOR and OLE ClinicalTrials.gov numbers, NCT02623699 and NCT03070119; EudraCT numbers, 2015-004098-33 and 2016-003225-41.).

Published
2022

4. Orofacial function and temporomandibular disorders in Parkinson's Disease:a case-controlled study

Author

Baram, Sara, Thomsen, Carsten Eckhart, Øzhayat, Esben Boeskov, Karlsborg, Merete, and Bakke, Merete

Subjects
Facial Pain, Humans, Parkinson Disease, Sialorrhea, Temporomandibular Joint Disorders, Awareness
Abstract

BACKGROUND: The difficulties and challenges faced by people with Parkinson's disease (PD) in performing daily orofacial function are not systematically investigated. In this study, specific orofacial non-motor and motor symptoms and functions were systematically examined in PD patients in comparison to a matched control group.METHODS: The clinical case-controlled study was conducted from May 2021 to October 2022 and included persons with PD and age- and gender-matched persons without PD. The participants with PD were outpatients diagnosed with PD at the Department of Neurology at Bispebjerg University Hospital in Copenhagen, Denmark. The participants underwent a systematic clinical and relevant self-assessment of the orofacial function and temporomandibular disorders (TMD). The primary outcomes were objective and subjective assessments of the general orofacial function, mastication, swallowing, xerostomia and drooling. The secondary outcomes were the prevalence of TMD and orofacial pain. The difference in outcome measures between the two groups was analysed using chi-square and Mann-Whitney U test.RESULTS: The study included 20 persons with PD and 20 age- and gender-matched persons without PD. Both objectively and subjectively, persons with PD had poorer orofacial function than the control group. Persons with PD had also a significantly more severe limitation of jaw mobility and jaw function. The objective masticatory function was also significantly reduced for persons with PD compared to the control group, and 60% of persons with PD found it difficult to eat foods with certain consistencies while 0% of the control group reported that problem. Persons with PD could swallow less water per second and the average swallowing event was significantly longer for PD persons. Even though PD persons reported more xerostomia (58% for persons with PD and 20% for control persons), they also reported significantly more drooling than the control group. Additionally, orofacial pain was more prevalent in PD persons.CONCLUSIONS: Persons with PD have a compromised orofacial function. Furthermore, the study indicates a link between PD and orofacial pain. In order to screen and treat persons with PD accordingly, healthcare professionals should be aware of and address these limitations and symptoms.TRIAL REGISTRATION: The trial was approved by the Regional Committee on Research Health Ethics of the Capital Region (H-20,047,464), the Danish Data Protection Agency (514 - 0510/20-3000), and registered at ClinicalTrials.gov (NCT05356845).

Published
2023

5. Missense dopamine transporter mutations associate with adult parkinsonism and ADHD

Author

Hansen, Freja H., Skjorringe, Tina, Yasmeen, Saiqa, Arends, Natascha V., Sahai, Michelle A., Erreger, Kevin, Andreassen, Thorvald F., Holy, Marion, Hamilton, Peter J., Neergheen, Viruna, Karlsborg, Merete, Newman, Amy H., Pope, Simon, Heales, Simon J.R., Friberg, Lars, Law, Ian, Pinborg, Lars H., Sitte, Harald H., Loland, Claus, Shi, Lei, Weinstein, Harel, Galli, Aurelio, Hjermind, Lena E., Moller, Lisbeth B., and Gether, Ulrik

Subjects
Genetic variation -- Identification and classification, Membrane proteins -- Genetic aspects, Parkinson's disease -- Genetic aspects -- Development and progression, Attention-deficit hyperactivity disorder -- Genetic aspects -- Development and progression, Health care industry
Abstract

Parkinsonism and attention deficit hyperactivity disorder (ADHD) are widespread brain disorders that involve disturbances of dopaminergic signaling. The sodium-coupled dopamine transporter (DAT) controls dopamine homeostasis, but its contribution to disease remains poorly understood. Here, we analyzed a cohort of patients with atypical movement disorder and identified 2 DAT coding variants, DAT-Ile312Phe and a presumed de novo mutant DAT-Asp421Asn, in an adult male with early-onset parkinsonism and ADHD. According to DAT single-photon emission computed tomography (DAT-SPECT) scans and a fluoro-deoxy-glucose-PET/MRI (FDG-PET/MRI) scan, the patient suffered from progressive dopaminergic neurodegeneration. In heterologous cells, both DAT variants exhibited markedly reduced dopamine uptake capacity but preserved membrane targeting, consistent with impaired catalytic activity. Computational simulations and uptake experiments suggested that the disrupted function of the DAT- Asp421Asn mutant is the result of compromised sodium binding, in agreement with Asp421 coordinating sodium at the second sodium site. For DAT-Asp421Asn, substrate efflux experiments revealed a constitutive, anomalous efflux of dopamine, and electrophysiological analyses identified a large cation leak that might further perturb dopaminergic neurotransmission. Our results link specific DAT missense mutations to neurodegenerative early-onset parkinsonism. Moreover, the neuropsychiatric comorbidity provides additional support for the idea that DAT missense mutations are an ADHD risk factor and suggests that complex DAT genotype and phenotype correlations contribute to different dopaminergic pathologies., Introduction Dopamine is an important neurotransmitter regulating motor activity, cognition, neuroendocrine functions, and reward mechanisms. Moreover, disturbances in dopaminergic signaling are of central importance in several common brain diseases including [...]

Published
2014
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6. Complement Profiles in Patients with Amyotrophic Lateral Sclerosis: A Prospective Observational Cohort Study

Author

Kjældgaard, Anne-Lene, primary, Pilely, Katrine, additional, Olsen, Karsten Skovgaard, additional, Øberg Lauritsen, Anne, additional, Wørlich Pedersen, Stephen, additional, Svenstrup, Kirsten, additional, Karlsborg, Merete, additional, Thagesen, Helle, additional, Blaabjerg, Morten, additional, Theódórsdóttir, Ásta, additional, Gundtoft Elmo, Elisabeth, additional, Torvin Møller, Anette, additional, Pedersen, Niels Anker, additional, Kirkegaard, Niels, additional, Møller, Kirsten, additional, and Garred, Peter, additional

Published
2021
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9. Collective physician perspectives on non-oral medication approaches for the management of clinically relevant unresolved issues in Parkinson's disease: Consensus from an international survey and discussion program

Author

Odin, P., Ray, Chaudhuri, Slevin, K., Volkmann, J. T., Dietrichs, J., Martinez Martin, E., Krauss, P., Henriksen, J. K., Katzenschlager, T., Antonini, Angelo, Rascol, A., Poewe, O., Brücke, W., Pirker, T., Ransmayr, W., Schwingenschuh, G., Tomantschger, P., Volc, V., Jespersen, D., Kamal, H., Karlsborg, A., Oppel, M., Pedersen, L., Avikainen, S., Kaasinen, S., Pekkonen, V., Ruottinen, E., Azulay, H., Corvol, J. P., Courbon, J. C., Defebvre, C. B., Durif, L., Houeto, F., Krack, J. L., Tison, P., Andrich, F., Ehret, J., Klostermann, R., Krüger, F., Lingor, R., Liszka, P., Schwarz, R., Timmermann, J., Warnecke, L., Bostantjopoulou, T., Konitsiotis, S., Papageorgiou, S., Stathishens, S., Stefanis, P., Zikos, L., Browne, P., Healy, P., Lynch, D., O'Riordan, T., O'Sullivan, S., Walsh, S., Abbruzzese, R., Lopiano, G., Modugno, L., Tamma, N., Holmberg, F., Linder, B., Nyholm, J., Pålhagen, D., Matías Arbelo, S., Bana, J., Castrillo, R. Y., Castro, J. C. M., e. Garcia Ruiz Espiga, A., Kulisevsky, P. J., Lezcano, J., Luquin, E., Mir, R., Puente, P., Valldeoriola, V., Burn, F., Clarke, D., Foltynie, C., Grosset, T., Hindle, D., Leake, J., Lees, A., Morris, A., Stewart, H., Walker, D., Worth, R., AbbVie, and Karlsborg, Merete

Subjects
medicine.medical_specialty, Parkinson's disease, Neurology, Consensus, Disease duration, Clinical Neurology, Non-motor symptoms, Disease, Surveys and Questionnaires, medicine, Humans, Device-aided therapies, Dyskinesias, Motor fluctuations, Orthopedic Equipment, Parkinson Disease, Medicine (all), Geriatrics and Gerontology, Neurology (clinical), Psychiatry, Cognitive impairment, Depression (differential diagnoses), business.industry, International survey, medicine.disease, Family medicine, business, Educational program
Abstract

Navigate PD was an educational program established to supplement existing guidelines and provide recommendations on the management of Parkinson's disease (PD) refractory to oral/transdermal therapies. It involved 103 experts from 13 countries overseen by an International Steering Committee (ISC) of 13 movement disorder specialists. The ISC identified 71 clinical questions important for device-aided management of PD. Fifty-six experts responded to a web-based survey, rating 15 questions as 'critically important;' these were refined to 10 questions by the ISC to be addressed through available evidence and expert opinion. Draft guidance was presented at international/national meetings and revised based on feedback. Key take-home points are: • Patients requiring levodopa >5 times daily who have severe, troublesome 'off' periods (>1-2 h/day) despite optimal oral/transdermal levodopa or non-levodopa-based therapies should be referred for specialist assessment even if disease duration is 70 years who have mild or moderate cognitive impairment, severe depression or other contraindications to DBS. Medical writing support was provided by Emma East and Lindy van den Berghe at Lucid Group and funded by AbbVie. Sí

Published
2015

10. [SOD1 gene therapy delays ALS disease progression].

Author

Forsberg K, Karlsborg M, Salvesen L, Svenstrup K, Winroth I, Berntsson H, and M Andersen P

Subjects
Humans, Male, Middle Aged, Mutation, Oligonucleotides, Antisense therapeutic use, Oligonucleotides, Antisense administration & dosage, Oligonucleotides therapeutic use, Oligonucleotides administration & dosage, Amyotrophic Lateral Sclerosis genetics, Amyotrophic Lateral Sclerosis drug therapy, Amyotrophic Lateral Sclerosis therapy, Superoxide Dismutase-1 genetics, Genetic Therapy, Disease Progression
Abstract

We present a patient with familial amyotrophic lateral sclerosis caused by an aggressive A4S mutation in the SOD1 gene. In 2020, the patient was enrolled in the VALOR SOD1 gene therapy phase-3 trial. At screening, the ALSFRS-R score was 41 (48 is normal) and the level of CSF-neurofilament L (an indicator of ongoing neuronal damage) was 11 000 ng/L (ref <650 ng/L). In the four years following enrollment, the patient received monthly intrathecal treatment with tofersen, an antisense oligonucleotide compound that inhibits SOD1 protein expression and hence lowers the synthesis of toxic SOD1 protein species. Side effects have been minimal and mostly attributed to the spinal taps. The patient remains ambulatory with an active social lifestyle. The ALSFRS-R score has in the past 18 months stabilized around 35-37, CSF-NfL is 1 290 ng/L and plasma-NfL is 12 (reference <13). This is the first documented arresting intervention in a patient with ALS in Sweden.

Published
2024

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