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

  • Erika F. AugustineEmail author
  • Christopher A. Beck
  • Heather R. Adams
  • Sara Defendorf
  • Amy Vierhile
  • Derek Timm
  • Jill M. Weimer
  • Jonathan W. Mink
  • Frederick J. Marshall
Research Report
Part of the JIMD Reports book series (JIMD, volume 43)


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.


Autoantibodies Autoimmunity Batten disease Clinical trial Immunosuppression Rare disease 



The trial was supported by research grants from the Batten Disease Support and Research Association and the Food and Drug Administration (#FD003908). We thank the study participants and their families for graciously sharing their time and support for the study. We also acknowledge the study contributions of the site investigators, medical monitors, and data safety monitoring committee.

Site Investigators

Kirk Agerson, MD; Angela Black, MD; Tom Byrne, MD; David Callahan, MD; Emily de los Reyes, MD; Greg Guerriero, DO; John Gunderman, MD; Donna Heffernan, MD; Raymond Hubbard, MD; Randa Jarrar, MD; Marian Kummer, MD; Dawn Marie Minyon-Sarver, DO; Young Oliver, MD; Wilfred Raine, MD; Katherine Sims, MD; Ayame Takahashi, MD; Sharmell Wilson, MD.

Medical Monitors

Jennifer Kwon, MD, University of Rochester Medical Center, Rochester, NY.

Laurie Seltzer, DO, University of Rochester Medical Center, Rochester, NY.

Data and Safety Monitoring Committee

Leon Dure, MD, University of Alabama, Birmingham, AL.

Marc Lande, MD, MPH, University of Rochester Medical Center, Rochester, NY.

Michael McDermott, PhD, University of Rochester Medical Center, Rochester, NY.


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Copyright information

© Society for the Study of Inborn Errors of Metabolism (SSIEM) 2018

Authors and Affiliations

  • Erika F. Augustine
    • 1
    • 2
    • 3
    Email author
  • Christopher A. Beck
    • 4
  • Heather R. Adams
    • 1
    • 2
  • Sara Defendorf
    • 5
  • Amy Vierhile
    • 1
    • 2
  • Derek Timm
    • 6
  • Jill M. Weimer
    • 6
  • Jonathan W. Mink
    • 1
    • 2
    • 7
  • Frederick J. Marshall
    • 1
  1. 1.Department of NeurologyUniversity of Rochester Medical CenterRochesterUSA
  2. 2.Department of PediatricsUniversity of Rochester Medical CenterRochesterUSA
  3. 3.Center for Health + TechnologyUniversity of Rochester Medical CenterRochesterUSA
  4. 4.Department of Biostatistics and Computational BiologyUniversity of Rochester Medical CenterRochesterUSA
  5. 5.Pharmaceutical Product Development (PPD)CharlotteUSA
  6. 6.Pediatrics and Rare Diseases GroupSanford ResearchSioux FallsUSA
  7. 7.Department of NeuroscienceUniversity of Rochester Medical CenterRochesterUSA

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