Immunosuppression alters disease severity in juvenile Batten disease mice

J Neuroimmunol. 2011 Jan;230(1-2):169-72. doi: 10.1016/j.jneuroim.2010.08.024.

Abstract

Autoantibodies to brain proteins are present in Juvenile Neuronal Ceroid Lipofuscinosis (Batten disease) patients and in the Cln3-/- mouse model of this disease, suggesting an autoimmune component to pathogenesis. Using genetic or pharmaceutical approaches to attenuate this immune response in Cln3-/- mice, we demonstrate decreased neuroinflammation, decreased deposition of immunoglobulin G in the brain and protection of vulnerable neuron populations. Moreover, immune suppression results in a significant improvement in motor performance providing for the first plausible therapeutic approach for juvenile Batten disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies / drug effects
  • Autoantibodies / immunology
  • Blotting, Western
  • Brain / drug effects*
  • Brain / pathology
  • Cell Count
  • Disease Models, Animal
  • Immunohistochemistry
  • Immunosuppression*
  • Immunosuppressive Agents / pharmacology*
  • Male
  • Membrane Glycoproteins / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Molecular Chaperones / genetics
  • Motor Skills / drug effects
  • Mycophenolic Acid / analogs & derivatives
  • Mycophenolic Acid / pharmacology
  • Neuronal Ceroid-Lipofuscinoses / drug therapy*
  • Neuronal Ceroid-Lipofuscinoses / immunology*
  • Neuronal Ceroid-Lipofuscinoses / pathology
  • Neurons / drug effects
  • Neurons / pathology

Substances

  • Autoantibodies
  • CLN3 protein, mouse
  • Immunosuppressive Agents
  • Membrane Glycoproteins
  • Molecular Chaperones
  • Mycophenolic Acid