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. 2019:43:117-124.
doi: 10.1007/8904_2018_113. Epub 2018 Jun 20.

Short-Term Administration of Mycophenolate Is Well-Tolerated in CLN3 Disease (Juvenile Neuronal Ceroid Lipofuscinosis)

Erika F Augustine  1   2   3 , Christopher A Beck  4 , Heather R Adams  5   6 , Sara Defendorf  7 , Amy Vierhile  5   6 , Derek Timm  8 , Jill M Weimer  8 , Jonathan W Mink  5   6   9 , Frederick J Marshall  5
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Short-Term Administration of Mycophenolate Is Well-Tolerated in CLN3 Disease (Juvenile Neuronal Ceroid Lipofuscinosis)

Erika F Augustine et al. JIMD Rep. 2019.

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.

Keywords: Autoantibodies; Autoimmunity; Batten disease; Clinical trial; Immunosuppression; Rare disease.

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Conflict of interest statement

EF Augustine, HR Adams, and JW Mink have received research support from Abeona Therapeutics. JW Mink has received consulting fees from Sumitomo, Inc. CA Beck, S Defendorf, A Vierhile, D Timm, JM Weimer, and FJ Marshall declare that they have no conflicts of interest.

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