Chapter title |
Short-Term Administration of Mycophenolate Is Well-Tolerated in CLN3 Disease (Juvenile Neuronal Ceroid Lipofuscinosis)
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Chapter number | 113 |
Book title |
JIMD Reports, Volume 43
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Published in |
JIMD Reports, January 2018
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DOI | 10.1007/8904_2018_113 |
Pubmed ID | |
Book ISBNs |
978-3-66-258613-6, 978-3-66-258614-3
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Authors |
Erika F. Augustine, Christopher A. Beck, Heather R. Adams, Sara Defendorf, Amy Vierhile, Derek Timm, Jill M. Weimer, Jonathan W. Mink, Frederick J. Marshall, Augustine, Erika F., Beck, Christopher A., Adams, Heather R., Defendorf, Sara, Vierhile, Amy, Timm, Derek, Weimer, Jill M., Mink, Jonathan W., Marshall, Frederick J. |
Abstract |
Mycophenolate, an immunosuppressant, is commonly used off-label for autoimmune neurological conditions. In CLN3 disease, a neurodegenerative disorder of childhood, preclinical and clinical data suggest secondary autoimmunity and inflammation throughout the central nervous system are key components of pathogenesis. We tested the short-term tolerability of mycophenolate in individuals with CLN3 disease, in preparation for possible long-term efficacy trials of this drug. We conducted a randomized, double-blind, placebo-controlled, crossover study of mycophenolate in 19 ambulatory individuals with CLN3 disease to determine the safety and tolerability of short-term administration (NCT01399047). The study included two 8-week treatment periods with a 4-week intervening washout. Mycophenolate was well tolerated. 89.5% of participants completed the mycophenolate arm, on the assigned study dose (95% CI: 66.9-98.7%), and there were no significant differences in tolerability rates between mycophenolate and placebo arms (10.5%; 95% CI: -3.3-24.3%, p = 0.21). All reported adverse events were mild in severity; the most common adverse events on mycophenolate were vomiting (31.6%; 95% CI: 12.6-56.6%), diarrhea (15.8%; 95% CI: 3.4-39.6%), and cough (15.8%; 95% CI: 3.4-39.6%). These did not occur at a significantly increased frequency above placebo. There were no definite effects on measured autoimmunity or clinical outcomes in the setting of short-term administration. Study of long-term exposure is needed to test the impact of mycophenolate on key clinical features and CLN3 disease trajectory. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 5 | 71% |
Burkina Faso | 1 | 14% |
Unknown | 1 | 14% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 6 | 86% |
Scientists | 1 | 14% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 26 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 5 | 19% |
Student > Master | 4 | 15% |
Student > Bachelor | 3 | 12% |
Student > Postgraduate | 3 | 12% |
Professor | 2 | 8% |
Other | 4 | 15% |
Unknown | 5 | 19% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 7 | 27% |
Biochemistry, Genetics and Molecular Biology | 4 | 15% |
Pharmacology, Toxicology and Pharmaceutical Science | 3 | 12% |
Nursing and Health Professions | 2 | 8% |
Neuroscience | 2 | 8% |
Other | 3 | 12% |
Unknown | 5 | 19% |