Session Type: ACR Concurrent Abstract Session
Session Time: 2:30PM-4:00PM
Background/Purpose: Treatment of autoimmune
diseases is still based on the use of general immunosuppressive drugs which
invariably cause severe side effects. This fact has compelled searches for more
specific or targeted delivery of drugs. Calcium/ calmodulin- dependent protein
kinase IV (CaMK4) is involved in the suppression of IL-2 and enhancement of IL-17
production and its pharmacologic or genetic inhibition limits disease
progression in lupus-prone mice and mice subjected to experimental allergic
Methods: EAE and lupus prone
(MRL/lpr) mice were treated with KN93 (an inhibitor of Camk4)- loaded
nanolipogels (nlg) targeted into CD4+ cells, and analyzed for immunologic and
Results: KN93 delivered with nlg
directly to CD4+ cells at an equivalent of one twentieth of the dose required systemically,
is clinically equally effective for both lupus and EAE. Specific delivery of
the CaMK4 inhibitor did not deplete T cells and did not suppress autoantibody
production but it effectively blocked Th17 cell expansion in the spinal cord
and the kidney of mice developing EAE or lupus respectively.
Conclusion: Inhibition of molecules
proven to be involved in the expression of autoimmunity only in relevant cells
is a highly promising way to advance treatment in autoimmune diseases.
Figure 1. The schema
of the structure of KN93 loaded nanolipogels (nlg) used in this work.
Figure 2. Average
clinical score of the mice treated with nlg- empty, anti CD4 antibody coated
nlg- empty (CD4- nlg- empty), nlg- KN-93 and CD4- nlg- KN-93 on EAE model (n =
8 mice in each group). The each nlg were injected weekly. Error bars represent
the mean ± SEM. **P<0.01 by 2way ANOVA.
Figure 3. The mean ratio of
urine albumin and creatinine from the MRL/lpr mice treated with free- KN-93,
anti CD4 antibody coated nlg- empty (CD4- empty) and anti CD4 antibody coated
nlg- KN93 (CD4- KN-93) (n = 4 mice in each group. Urine samples were obtained
biweekly and determined by albumin and creatinine ELISA. Error bars represent
the mean ± SEM. *P<0.05 by 2way ANOVA.
To cite this abstract in AMA style:Otomo K, Koga T, Yoshida N, Mizui M, Kriegel C, Fahmy T, Tsokos GC. Nanogel Based Delivery of an Inhibitor of Calcium/ Calmodulin- Dependent Protein Kinase 4 Suppresses Experimental Autoimmune Encephalomyelitis and Lupus-like Disease in Mice [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/nanogel-based-delivery-of-an-inhibitor-of-calcium-calmodulin-dependent-protein-kinase-4-suppresses-experimental-autoimmune-encephalomyelitis-and-lupus-like-disease-in-mice/. Accessed October 27, 2021.
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